Invest Clin 64(3): 338 - 354, 2023 https://doi.org/10.54817/IC.v64n3a7

Corresponding author: Oralia Nájera Medina. Departamento de Atención a la Salud, División de Ciencias Básicas

y de la Salud, Universidad Autónoma Metropolitana Unidad Xochimilco (UAM-Xochimilco), Ciudad de México, Mé-

xico. Phone: (+52) (55) (5483 7000, ext. 2675. Email: onajera@correo.xoc.uam.mx

Modified High-Intensity Interval Training

and its effects on immunometabolic

regulation in sedentary young adults with

overweight and obesity.

Carmen Paulina Rodríguez-López

, María Cristina González-Torres

and Oralia Nájera-Medina

Departamento de Atención a la Salud, CBS, Universidad Autónoma Metropolitano-

Xochimilco (UAM-Xochimilco), Ciudad de México , México.

Departamento de Ciencias de la Salud, CBS, UAM-Iztapalapa, Ciudad de México,

México.

Keywords: obesity; physical activity; lymphocytes; metabolic syndrome; visceral fat.

Abstract. Sedentary lifestyles can contribute to obesity and other diseas-

es; while chronic low-grade inflammation associated with obesity can lead to

metabolic alterations. As physical activity is an alternative to decrease excess

weight and its related comorbidities, High-Intensity Interval Training (HIIT) has

recently emerged as effective in regulating whole-body metabolism and inflam-

matory processes in people with excess weight. The objective was to compare

the effects of a modified HIIT program on peripheral blood leukocytes (PBL),

metabolic profile, insulin resistance (IR), and body composition (BC) in sed-

entary adults with excess weight. PBL, biochemical variables, IR, and BC were

analyzed in 37 participants, 23 sedentary young adults (17 with overweight

and six with obesity), before and after eight weeks of a modified HIIT program

and compared with those of 14 healthy-weight participants. The results showed

that after HIIT, total lymphocytes, TCD3+, and TCD8+ lymphocytes decreased;

granulocytes and naïve TCD3+ cells increased in patients. Regarding partial

correlations, we found that changes (Δ) in TCD8+ lymphocytes correlated posi-

tively with glucose and LDL-c, while naïve TCD3+ cells correlated with total

cholesterol and LDL-c. Δ in TCD4+CD45RA+ cells correlated negatively with Δ

in subcutaneous fat tissue and body fat mass. This study reports that sedentary

young adults who completed the modified HIIT program showed lymphocyte

levels similar to those in healthy-weight individuals and positive changes in the

study variables. Such changes suggest immunometabolic regulation through

the implementation of HIIT in participants with overweight and obesity.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 339

Vol. 64(3): 338 - 354, 2023

Entrenamiento modificado de intervalos de alta intensidad

y sus efectos sobre la regulación inmunometabólica en adultos

jóvenes sedentarios con sobrepeso y obesidad.

Invest Clin 2023; 64 (3): 338 – 354

Palabras clave: obesidad; actividad física; leucocitos; síndrome metabólico; grasa

visceral.

Resumen. El sedentarismo puede contribuir a obesidad y otras enfermeda-

des; la

inflamación crónica de bajo grado asociada a la obesidad puede llevar a

alteraciones metabólicas. La actividad física es una alternativa para disminuir

el exceso de peso y sus comorbilidades asociadas, donde el Entrenamiento de

Intervalos de Alta Intensidad (HIIT, por sus siglas en inglés) ha emergido como

un regulador del metabolismo del cuerpo y del proceso inflamatorio en personas

con exceso de peso. El objetivo de esta investigación fue analizar los efectos del

programa de HIIT modificado sobre leucocitos en sangre periférica (LSP), perfil

metabólico, resistencia a la insulina y composición corporal (CC) en 37 partici-

pantes, 23 con exceso de peso (17 con sobrepeso y 6 con obesidad), después de

ocho semanas del entrenamiento y compararlos con 14 participantes con peso

saludable. Se encontró que los linfocitos totales, linfocitos TCD3+ y TCD8+

disminuyeron; los granulocitos y las células TCD3+ vírgenes aumentaron. En

cuanto a las correlaciones parciales, encontramos que los cambios (Δ) en los

linfocitos TCD8+ se correlacionaron positivamente con la glucosa y LDL-c,

mientras que las células TCD3+ vírgenes correlacionaron con colesterol total

y LDL-c. Δ en células TCD4+CD45RA+ correlacionaron negativamente con Δ

en tejido adiposo subcutáneo y masa grasa corporal. Estos resultados mostra-

ron que los adultos sedentarios que completaron el entrenamiento presentaron

niveles de linfocitos similares a los de los participantes con un peso saludable y

cambios positivos en las variables de estudio. Tales cambios sugieren una regu-

lación inmunometabólica en los participantes con sobrepeso y obesidad.

Received: 20-12-2022 Accepted: 27-04-2023

INTRODUCTION

About one-third of the world popula-

tion aged 15 years and older do not engage

in sufficient physical activity. Consequently,

health risks associated with a sedentary life-

style are on the rise. Sedentary lifestyles and

behaviors have several negative effects on

the human body including, ‘risks of meta-

bolic disorders such as diabetes mellitus, hy-

pertension, and dyslipidemia’

Obesity has been considered a chronic

low-grade inflammatory process character-

ized by an increase in the baseline number

of leukocytes and an imbalance between pro-

and anti-inflammatory cytokines in circula-

tion

2-4

. Such a condition is associated with

insulin resistance (IR)

, which is character-

ized by impaired insulin function in meta-

bolically essential tissues, affecting lipid ho-

meostasis and glucose and contributing to

metabolic disorders

6,7

340 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

It has been proposed that weight gain

and its related comorbidities can be re-

versed through caloric restriction and in-

creased physical activity

. In addition, it has

been found that relative health benefits can

emerge even in those cases in which there is

no change in total sedentary time but inter-

mittent physical activities are included

. In

this respect, it has been observed that regu-

lar exercise is an effective measure against

chronic diseases as it improves the inflam-

matory profile

Recently, modern lifestyles have in-

creasingly promoted sedentary behavior

also among young adults. Against this back-

ground, High-Intensity Interval Training

(HIIT) has emerged as an alternative that

‘burns many calories in a short time, so

busy people can be more inclined to incor-

porate intermittent bursts of exercise into

their schedule’

. HIIT effectively regulates

whole-body metabolism

11,12

, enhances insu-

lin signaling, and improves anthropometric

measures and body composition (BC)

13-14

. In

addition, HIIT has been associated with im-

munomodulatory effects with potential anti-

inflammatory benefits

Although positive effects of HIIT have

been reported concerning obesity, little is

known about the relationship between dif-

ferent variables like body composition, met-

abolic profile, lymphocyte subpopulations,

and inflammatory response. Because the

problem of obesity has grown in recent years

and it is presented as a complex condition to

treat and because it implies lifestyle chang-

es, it is necessary to propose strategies to the

population that, in the short term, provide

them with some benefit, which is observable

as physical activity. Therefore, this study

aimed to investigate the effects of a modi-

fied HIIT program over eight weeks on the

variables mentioned above, peripheral blood

cells, metabolic profile, IR, anthropometric

measures, and BC in apparently healthy sed-

entary patients with overweight or obesity,

with or without metabolic syndrome (MS).

METHODS

Study design

A longitudinal clinical-trial study was

performed with sedentary young adults in

Mexico City, Mexico. The study was conduct-

ed following the Declaration of Helsinki,

and the protocol was approved by the Eth-

ics Committee of the Metropolitan Autono-

mous University of Xochimilco (Agreement

13/16,8.1). Participants provided written in-

formed consent before enrolling in the study.

The study population was selected ac-

cording to the following criteria:

Inclusion criteria: adults aged 18-40

years apparently healthy with overweight

(OW) or obesity (Ob) who did not engage in

regular and sufficient physical activities.

Exclusion criteria: individuals with any

infection, pregnant women, individuals with

diabetes mellitus type 1 or type 2 (DM2), or

autoimmune, hepatic, renal, endocrine, can-

cer, or heart disease, who were taking any

medication and/or participating in regular

exercise training, and who did not present a

medical certificate to engage in regular ex-

ercise.

The program included no dietary or ali-

mentary behavior modification to minimize

the influence of additional factors. All the

variables listed below were assessed before

and after two months of modified HIIT work-

outs. Measures were taken after at least 48 h

of the last exercise session to avoid data on

the acute effects of exercise. All the variables

listed below were evaluated at the beginning

and after two months (eight weeks) under a

modification of the HIIT training.

Se dentary behavior

Sedentary behavior was evaluated us-

ing an International physical activity ques-

tionnaire (IPAQ)-short form (7-day physical

activity). All participants were required to

complete the questionnaire in advance of the

study. An IPAQ activity level of <600 MET/

week was defined as sedentary behavior.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 341

Vol. 64(3): 338 - 354, 2023

Clinical measurements

Anthropometric measurements were

performed following the standardized pro-

tocol of the International Society for the

Advancement of Kinanthropometry (ISAK)

(Although the person who made the mea-

surements for the study is not ISAK certi-

fied, it was standardized by someone who

is ISAK certified). A SECA 213 stadiometer

set at 0.1 cm of precision was used to mea-

sure height. Weight was measured using

InBody720 equipment (Biospace, Inc. Los

Angeles, CA, USA), and waist circumference

(WC) was measured employing SECA brand

201 (Chino, CA, USA) fiberglass tape. Nutri-

tional status was assessed through body mass

index (BMI) according to the World Health

Organization (WHO)

criteria for adults.

A dual-energy X-ray absorptiometry

(Hologic Discovery Wi. Hologic, Inc. Bed-

ford, MA, USA) was used to measure body

composition, obtaining data on skeletal

muscle mass (SMM, in kg), body fat mass

(BFM, in kg) and the percentage of body fat

(BF%). A multi-frequency impedance body

composition analyzer (InBody 720, equip-

ment) was utilized to obtain visceral adipose

tissue (VAT) in square meters, in which vis-

ceral obesity (increased VAT) was diagnosed

in persons with ≥100 cm

of fat and normal

VAT in persons with <100 cm

of fat).

Lipid and glucose measurements

For biochemical tests, 5 mL of a venous

blood sample was collected using an auto-

mated clinical chemistry equipment KON-

TROLab, model Ikem (KONTROLab Co., Ltd.

Roma, Italia), to obtain: triglycerides (TG);

high-density lipoprotein-cholesterol (HDL-

c), fasting glycemia (Glu), and total choles-

terol (TCho). Low-density lipoprotein-cho-

lesterol (LDL-c) was calculated based on the

Friedewald formula. Samples were obtained

after a 12-h fasting period. Blood pressure

measurements were performed according to

the guidelines of the Mexican Official Norm

(NOM-030-SSA2-1999). The presence of MS

was determined according to the Choles-

terol Education National Program (ATP III)

definition and modified according to the

Hispanic population

. These guidelines sug-

gest that MS is present when an association

of at least three of the following factors is

found: TG ≥150 mg/dL; HDL-c <40 mg/dL;

blood pressure ≥130/85 mmHg or a previ-

ous diagnosis; Glu ≥100 mg/dL, and a WC

in women of ≥80 cm and in men ≥90 cm.

Insulin resistance

The METabolic Scale for Insulin Resis-

tance (METS-IR) tool was employed to mea-

sure the IR parameter. This consists of an

indirect method for the detection of insulin

action that takes into account blood concen-

trations of TG, HDL-c, glucose, and BMI as

follows: (Ln((2*G0)+TG0)*IMC)/(Ln(HDL-

c)); G0: fasting glucose, and TG0: fasting

triglycerides

Measurement of lymphocyte

subpopulations

A 5 mL venous blood sample was collected

in tubes containing K

EDTA (BD Biosciences,

San Jose, CA, USA). Cells were stained with con-

jugated commercial antibodies (BD Bioscienc-

es, San Jose, CA, USA), and the combinations

employed were the following: FITC-anti-IgG1/

PE-anti-IgG2; FITC-anti-CD45/Pe-anti-CD14;

FITC-anti-CD3/PE-anti-CD16+CD56/PerCP-

anti-CD19; FITC-anti-CD4/PE-anti-CD62/

APC -anti-CD3; FITC-anti-CD8/PE-anti-CD28/

APC-anti-CD3, and FITC-anti-CD45RA/PE-

anti-CD45RO/PerCP-anti-CD4/APC-anti-CD3.

Peripheral blood samples were stained with

conjugated antibodies for 20 min in the dark,

then 3 mL of lysis buffer solution was added.

Samples were washed (PBS), fixed with 1%

p-formaldehyde, and analyzed within 24 h of

staining

4, 19

.Cell analysis was performed using

a FACSCanto II Cytometer with FACSDiva soft-

ware (BD Biosciences, San Jose, CA, USA). For

each sample, 10,000 cells were counted.

Intervention

HIIT group participants were super-

vised along three HIIT exercise sessions per

342 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

week for eight weeks. Each training session

consisted of 25 min of effective exercise, and

each minute was divided into 30-s intervals

of activity, followed by a 30-s of active rest

(Active rests refers to the participants did

not stop moving altogether; they continued

jogging; it was rest from the exercises in-

volved in the session, such as squats or some

other exercise). Effective exercise time and

intervals increased according to the partici-

pants’ capacity. Eventually, the exercise ses-

sion consisted of 45 min of active exercise,

while each minute consisted of 50-s intervals

of activity, followed by 10-s of active rest. On

the recommendation of the Centers for Dis-

ease Control and Prevention, the American

College of Sports Medicine, and the Ameri-

can Heart Association

, sessions were orga-

nized into three parts.: warm-up (5-9 min),

aerobic part/resistance (HIIT) (25-45 min),

and cooling/flexibility (8-12 min).The ac-

tivity intensity was measured according to

the Perceived Exertion Rating Scale (RPE),

managed at moderate intensity (between 5

and 6)

. As HIIT works with high-intensity

intervals and since we worked with seden-

tary subjects with overweight and obesity,

a modification to this training system was

introduced in order to work at moderate in-

tensity. In addition, the Karvonen formula

(Functional Capacity Evaluation [FCE]=

{(FM-FR)*PI} + FR) was adapted, and the

percentage of intensity (PI) at which partici-

pants worked was obtained by taking into

account heart rate (FCE), resting frequency

(RF), and maximal frequency (MF) during

the training sessions)

. For the latter, the

FC was taken at each session before and af-

ter the training.

The participants’ adherence to the

study was calculated as the percentage of

complete sessions attended in relation to

the total number of training sessions pro-

posed in the present study.

Statistical analysis

The Shapiro‒Wilk test was utilized to

determine whether the variables presented

had a Gaussian distribution. Logarithmic

transformation was performed to calculate

the normality in variables without Gauss-

ian distribution. The results are presented

as means ± standard deviations (SD) and

medians, employing an interquartile range

(IQR, 25-75). Paired Student t-tests were

employed to compare pre-and post-exer-

cise data. The One-way analysis of variance

(ANOVA) and Bonferroni post-hoc tests were

applied to determine differences between

>two groups. Data were adjusted for gender

and age. Bilateral partial correlation analy-

ses adjusted for gender, age, and BMI were

performed to estimate the correlation of the

Δ of the lymphocyte subpopulations with the

Δ of the anthropometric, BC, and biochemi-

cal variables. Then, step-wise forward linear

regression models utilizing the Δ of lym-

phocyte subpopulations as dependent vari-

ables to evaluate the association with Δ of

anthropometric, BC, and biochemical vari-

ables adjusted for gender, age, and BMI were

performed. A p<0.05 was considered signifi-

cant, using the IBM SPSS ver. 21 statistical

software program.

RESULTS

Forty overweight or obese persons were

accepted to participate in the training ses-

sions; however, several individuals withdrew

from the exercise (n=11). In addition, six in-

dividuals did not attend their second evalu-

ation. Thus, the study group consisted of 23

individuals. Remarking this way, the problem

that sedentary people have of adhering to a

routine.

Thirty-seven people participated, and

two groups were formed: 1) the control

group, consisting of 14 participants with

normal BMI, normal weight (NW), and VAT,

without MS, matched by gender and age with

the study group, who did not perform train-

ing, and 2) the study group, consisting of

23 persons with OW and Ob who underwent

the training. All participants included in the

study attended at least 80% of the classes

High-Intensity Interval Training improves immunometabolism in sedentary obesity 343

Vol. 64(3): 338 - 354, 2023

conducted. The average age of participants

was 26.4±6.5 years, and 73% were female.

Baseline characteristics

Thirty-seven percent of participants

(n=14) had normal BMI, 46% (n=17) peo-

ple with OW, and 16% (n=6) had Ob. A

prevalence of 26% (n=6) of MS was found

in the study group. It was also observed that

individuals with MS were mostly people with

visceral obesity.

Laboratory analysis, anthropometric

measurements, and BC

Regarding biochemical variables, it was

observed that persons with obesity had the

highest TG values compared to individuals

with NW and diastolic pressure in relation

to individuals with OW. It was also found

that HDL-c was lower in individuals with OW

than in those with NW. Concerning IR, it was

found that METS-IR increased as the BMI

did; therefore, individuals with NW present-

ed the lowest values and persons with Ob the

highest values; these differences were signif-

icant (Table 1).

Concerning anthropometric measure-

ments and BC, it was found that participants

with NW had the lowest values in WC, ST,

BFM, and VAT compared to individuals with

OW or Ob (Table 1).

Lymphocyte subpopulations

It was found that total lymphocytes

(TL) increased according to BMI. On the

other hand, granulocytes were lower in per-

sons with NW when compared with individu-

als with OW or Ob; all of these differences

were statistically significant. No significant

differences were observed when analyzing

the memory and naïve cells according to nu-

tritional status (Table 2).

Intervention

Overall, participants worked at 54 ±

10.6% of their maximal level according to the

formula of Karvonen. In addition, the inten-

sity percentage was increased as the training

weeks progressed, finding a significant dif-

ference between weeks 1 and 6 (46±13 vs.

61.9±10%, p<0.05).

Laboratory analysis, anthropometric

measurements, and BC

In individuals with OW or Ob, no sig-

nificant positive changes were found in bio-

chemical indicators after training by group

(Table 1). However, when each participant

was analyzed, it was found that TG decreased

in 39% of the participants by 25±14.7%, Glu

in 61% by 22±10%, TCho in 74% of individu-

als by 24±10%, LDL-c in 74% by 37±16%,

and HDL-c increased in 52% of persons by

20±10% (Fig. 1).Regarding anthropometric

measurements and BC after training, persons

with OW presented a statistically significant

decrease in WC (Table 1). Also, when each

participant was analyzed, it was found that

VAT decreased in 57% of the participants by

5.3±4.6cm

, ST in 57% by 1.9±2.2%, BFM

in 61% of individuals by 1.7±1.5kg, and

SMM increased in 30% by 1.3±1.6kg (Fig.

2). In addition, it was observed that one per-

son with Ob passed to OW and two with OW

passed to NW; furthermore, two persons with

increased VAT passed to normality.

Lymphocyte subpopulations

After training, TL and TCD8+ lympho-

cytes decreased in the study group. Also,

granulocytes and näive TCD3+ cells in-

creased.

When the subpopulations were analyzed

according to BMI, TL, TCD3+, and TCD8+

decreased in individuals with OW, approach-

ing the percentages of persons with NW. In ad-

dition, an increase of TCD3+CD45RA+ and

monocytes was found in persons with OW. All

of these differences were statistically signifi-

cant (Table 2). According to MS, we found that

TCD4+ lymphocytes decreased (55.6±13.2 vs.

29±13%; p<0.0001) after the training activ-

ity. In individuals without MS, the monocytes

increased (6.6±3.5 vs. 8.2±2.4%; p<0.0001),

while TCD8+ lymphocytes decreased (39±8.5

vs. 29.8±11.8%; p<0.05).

344 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

Table 1

Biochemical indicators, anthropometric measurements, and body composition according to Body Mass Index

before and after two months of High-Intensity Integral Training.

Variable

(n=37)

Normal (n=14) Overweight (n=17) Obesity (n=6) p (ANOVA)

B A p# B A p# p

p (post

hoc)*&

TG (mg/dL) 80 ±26.5 119.8±52.6* 150.5±70.8 0.088 163.1±42.3* 187.3±58.9 0.188 0.002 0.002

c-HDL (mg/dL) 51.9 ±13.6 39.2* ±8.1 38.2 ±8.4 0.607 43.2 ±13.3 40.5 ±3.9 0.477 0.011 0.009

Glu (mg/dL)

81.1

(77.6-85.7)

79.4

(70.2-94.3)

83.8

(57.6-95.9)

0.597

81.2

(72.9-103.8)

78.7

(72.2-88.4)

0.226 0.754

c-LDL (mg/dL)

80.3

(64.9-93.6)

91.6

(60.9-130.3)

63.6

(46.4-88.7)

0.124

80.2

(46.7-144.1)

83.9

(48.1-99)

0.818 0.631

TCho (mg/dL)

146.9

(133.8-166.8)

161.7

(128.4-193.9)

140.2

(114-173.5)

0.608

165.3

(115.5-228.1)

156.9

(130.8-182.5)

0.757 0.628

SBP (mmHg) 105.5 ± 8.6 106.2 ±10.8 107 ±6.8 0.819 116.3 ±15.6 111.6 ±11.6 0.309 0.144

DBP (mmHg) 69.5 ±7 69.5 ±7.8 73.5 ±9.9 0.151 79 ±10.3& 76.6 ±5.1 0.675 0.049 0.059

METS-IR 31.8 ±4.2 42.4 ±4.9* 43 ±43 0.494 52 ±6.6*& 51.6 ±6.4 0.712 0.000 0.001

Weight (kg) 60.9 ±9.9 76.3 ±10* 75.9 ±10.4 0.328 87.1 ±17.5* 86.7 ±18.2 0.436 0.000 0.000

BMI (kg/m

) 22.5 ±1.7 27.3 ±1.3* 27.2 ±1.6 0.304 33.2 ±2.3*& 32.5 ±2.5 0.242 0.000 0.000

WC (cm) 81.2 ±7.4 90.9 ±6.4* 88.7 ±6.5# 0.001 102.7 ±10.5*& 99.7 ±11.2 0.187 0.000 0.000

SMM (kg) 23.8 (18.5-26.2) 26.3 (23.1-30.1) 26.6 (24.4-29.6) 0.949 23 (21.8-37) 23.6 (22-37.6) 0.131 0.150

ST (%) 27.7 ±6 35.5 ±5.9* 35 ±5.6 0.473 43.5 ±6.4*& 42.3 ±6.2 0.187 0.000 0.000

BFM (kg) 16.8 ±3.2 27 ±5.3* 27.2 ±6.8 0.822 37.1 ±3.8*& 36 ±4.7 0.258 0.000 0.000

VAT (cm

) 67.1 ±19 99.5 ±18* 98.5 ±18.8 0.500 139.9 ±28.6*& 138.5 ±33 0.722 0.000 0.000

Data are presented in media ± SD or median and interquartile range (IQR). p (post hoc): p adjusted with the Bonferroni test. # Statistically significant

difference between before and after. * Statistically significant difference vs normal. & Statistically significant difference vs overweighs (p<0.05). B: before;

A: after; TG: triglycerides; c-HDL: high-density lipoprotein cholesterol, Glu: glucose; c-LDL: Low-density cholesterol; TCho: total cholesterol; SBP: systolic

blood pressure; DBP: diastolic blood pressure; WC: waist circumference; SMM: skeletal muscle mass; ST: subcutaneous adipose tissue; BFM: body fat mass; VAT:

visceral adipose tissue.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 345

Vol. 64(3): 338 - 354, 2023

Table 2

Leukocyte distribution before and after High-Intensity Integral Training according to Body Mass Index

Variable (n=34)

(%)

Normal

(n=11)

Overweight

(n=17)

Obesity

(n=6)

B A p# B A p# P*&

Total lymphocytes 29.3 ±10.9 40.3 ±9.6* 32.2 ±8.5# 0.048

53.5

±9*&

33.1±7.5# 0.029 0.000

Monocytes 7.8 ±2.4 7.1 ±3.1 8.4 ±2.2# 0.044 5.6 ±2.5 5.9 ±1.3 0.893 0.256

Granulocytes 62.6±11.1 52.4 ±8.5* 59.1±8.2 0.064 40.9±8.7* 60.7 ±6.6# 0.014 0.000

Lymphocytes B

7.5

(5-12.6)

7.4

(5.4-10.5)

9.2

(6.1-1.7)

0.148

11.6

(7.7-18.8)

15.2

(9.9-18.6)

0.293 0.202

Lymphocytes NK

19.5

(12.8-32.7)

14.3

(10.6-19.9)

16.6

(14.2-24)

0.171

(9.4-19.8)

(16.2-26.7)

0.199 0.430

TCD3+ 68.4 ±10.6 76.5 ±8.1 68.9±10.5# 0.043 71.2±10.9 62 ±9.3 0.244 0.112

TCD4+

56.9

(46-60.7)

52.2 ±7.7 43.5 ±16.5 0.139 51.4±13.7 38.4 ±19.5 0.568 .763

TCD8+ 29.8 ±14.9 38.7 ±7.8 29.6±12.1# 0.002 34 ±7.4 24.1±11.1 0.147 0.198

TCD3+CD45RA+ 54.2 ±13 48.5 ±11.6 53.4 ±8.7# 0.050 44.5±18.7 59 ±15.6 0.330 0.456

TCD3+CD45RO+ 32.1 ±9.4 31.6 ±8.7 31.4 ±5.8 0.792 39.7±14.9 26.1±9.5 0.230 0.358

TCD3+CD45RO+

CD45RA+

15.7 ±6 16.7 ±5.9 12.7 ±6.6 0.454 14.6 ±5.8 11.6 ±6.7 0.558 0.828

TCD4+CD45RA+ 36.4 ±14.7 20.3 ±7.2 35 ±17.3 0.438 33.9 ±5.1 52.5 ±15.2 0.160 0.521

TCD4+CD54RO+ 43.2 ±13.4 48.1 ±8.8 53.1 ±20.6 0.712 43 ±20.6 36 ±12.7 0.661 0.796

TCD4+

CD45RO+CD45RA+

17.6 ±5.8 16.7 ±6.1 11.5 ±3.8 0.250 24.4±15.4 11.8 ±5.7 0.444 0.395

Data are presented in means ± SD or median and interquartile interval (IIC).* Statistically significant difference vs normal. & Statistically significant diffe-

rence vs. overweight. # Statistically significant difference before vs. after (p<0.05). B: before; A: after; Lymph B: Lymphocytes B; Lymph NK: Lymphocytes

natural killer.

346 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

Partial correlations were made of the ob-

served variations in leukocyte cells after the

intervention concerning the changes (Δ) in

the different variables, adjusting the analysis

by gender, age, and BMI. We found that Δ at

the peripheral level of the granulocytes and

TCD8+ lymphocytes correlated negatively

with Δ in WC; additionally, the Δ of TCD8+

lymphocytes correlated positively with glu-

cose and LDL-c. The Δ of the total näive

cells correlated positively with TCho and

LDL-c, and the Δ of the positive double cells

of TCD3+ (TCD3+CD45RA+CD45RO+)

positively correlated with the Δ in MERS-

IR. Last, the Δ of the näive cells of TCD4+

lymphocytes correlated negatively with the Δ

Fig. 1. Distribution and improvement of biochemical indicators after training.

Fig. 2. Distribution and improvement of anthropometric measurements and body composition after training.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 347

Vol. 64(3): 338 - 354, 2023

percentage and kilograms of fat, all of these

differences statistically significant (Table 3).

No correlation was observed between exer-

cise intensity and change in lymphocyte sub-

populations.

Furthermore, we decided to perform a

linear regression adjusted for gender, age, and

BMI among the changes in lymphocyte sub-

populations statistically correlated with the

changes in the different variables. A positive

correlation was found between the changes of

TCD8+ lymphocytes and TCD3+CD45RA+

lymphocytes with changes in LDL-c, where a

decrease of 1 mg/dl of this cholesterol was

associated with a decrease of 3% (range, 0.8-

4.5%) of TCD8+ lymphocytes and an increase

of 6% (range, 2.8-9.6%) of TCD3+CD45RA+

lymphocytes. Also, TCD3+CD45RA+ lympho-

cytes correlated positively with TCho, where a

decrease of 1 mg/dL of this type of choles-

terol was associated with an increase of 7%

(range, 1-11%) of TCD3+CD45RA+ lympho-

cytes. Finally, TCD3+CD45RA+CD45RO+

lymphocytes correlated positively with METS-

IR, where a decrease of 1 unit of METS-IR was

associated with a decrease of 1% (range, 0.5-

2%) of TCD3+CD45RA+CD45RO+ lympho-

cytes (Fig. 3).

DISCUSSION

Obesity is caused by a genetic predis-

position and environmental and lifestyle

factors, including physical inactivity and

poor eating habits

. Physical inactivity and

obesity are associated with visceral fat accu-

mulation, leading to chronic low-grade in-

flammation and the pathogenesis of IR, MS,

DM2, cardiovascular diseases, and cancer

24,25

Total sedentary time and moderate-to-

vigorous physical activity have been reported

to be negatively correlated. Waist circumfer-

ence, body mass index, triglyceride level, and

plasma glucose level have also been reported

to decrease while the number of breaks in

sedentary time increased

. On that basis,

the present study aimed at determining the

impact of a modified HIIT on metabolic, an-

Table 3

Partial correlation between changes in leukocyte cells and changes in the anthropometric,

biochemical, and body composition variables.

Leukocyte cells Variables

Δ of Total lymphocytes Δ of WC 0.491 0.053

Δ of granulocytes Δ of WC -0.514 0.041*

Δ of lymphocytes TCD8+ Δ of WC -0.612 0.007*

Δ of Glu 0.474 0.047*

Δ of DBP 0.458 0.056

Δ of c-LDL 0.617 0.006*

Δ of Total Cho. 0.460 0.055

Δ of TCD3+CD45RA+ Δ of c-LDL 0.959 0.010*

Δ of Total Cho. 0.941 0.017*

Δ of TCD3+CD45RA+CD45RO+ Δ of METS-IR 0.962 0.009*

Δ of TCD4+CD45RA+ Δ of ST -0.950 0.050*

Δ of BFM -0.974 0.026*

Δ of c-HDL 0.938 0.062

WC: waist circumference; Glu: glucose; DBP: diastolic blood pressure; c-LDL: Low-density cholesterol; Total Cho:

total cholesterol; ST: subcutaneous adipose tissue; BFM: body fat mass; c-HDL: high-density lipoprotein cholesterol.

p: p value adjusted by gender, age, and BMI (p<0.05).

348 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

Fig. 3. Linear regression between changes in leucocytes cells and changes of the different variables.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 349

Vol. 64(3): 338 - 354, 2023

thropometric, BC, and PBL measures in sed-

entary patients with OW and Ob.

HIIT has been proposed as a better-

suited activity for people with OW and Ob

than traditional continuous exercise

. Some

studies have reported a reduction in fasting

glucose, insulin, diastolic blood pressure

(DBP), and systolic blood pressure (SBP)

and improvements in insulin sensitivity af-

ter 16, 14, 12, or 2 weeks of HIIT

3, 26-29

. In

the present study, about 74% of participants

showed improvements in TG, Glu, TCho,

LDL-c, and HDL-c levels after training. Con-

cerning BC, other studies that implement-

ed HIIT in persons with OW or Ob for two

and 12 weeks, found a reduction in weight,

WC, fat mass, and BMI

27, 29

. In this study,

a significant statistical reduction was ob-

served only in WC in persons with OW, as

well as about 50% of participants showed de-

creased VAT (5.3±4.6cm

), ST (1.9±2.2%),

and BFM (1.7±1.5kg), and increased SMM

(1.3±1.6kg).

Although participants were untrained

people, they reached moderate intensity

during weeks 6 and 7 (62% of their inten-

sity percentage). The intensity percentage

increased as weeks progressed, observing a

significant difference between week 1 and

week 6 (p<0.05).

On the other hand, physical activity has

been often recognized as a powerful counter-

measure to inflammation

. A study carried

out with untrained young adults who par-

ticipated in HIIT for three days found that

the percentages of TCD4+, TCD8+, and

CD19+ lymphocytes increased significantly

after training

. Another study carried out

over two weeks with inactive persons with

OW or Ob revealed that training did not af-

fect the blood concentration of total lym-

phocytes (TL), monocytes, and neutrophils

. Both data do not coincide with those re-

ported in the present study, as it was found

that in persons with OW, TL, TCD3+, and

TCD8+ decreased (averages were similar

to those in persons with NW). On the other

hand, in individuals with Ob, TL decreased,

and granulocytes increased statistically, get-

ting closer to those values in persons with

NW. With these results, it can be observed

that only TL had the same behavior both in

individuals with OW and in those with Ob.

These data suggest differences in the mobili-

zation of leukocytes at the peripheral blood

level according to the nutritional status af-

ter physical activity.

In addition, it has been reported that

T lymphocytes and TCD8+ increase with

obesity

32, 33

and that they infiltrate adipose

tissue and promote the classical pro-inflam-

matory activity of M1 macrophages and the

production of pro-inflammatory cytokines.

These phenomena can trigger a metabolic

imbalance, such as an increase in Glu, TCho,

LDL-c, and TG and a decrease in HDL-c,

among others

34-36

. The finding in the present

study of diminished TL, TCD3+, and TCD8+

might indicate a decrease of the inflamma-

tory process at the peripheral blood level,

improving the metabolic profile, because

the improvement was found in the different

metabolic variables in a little more than 70%

of the participants, in addition, in different

correlations and linear regressions, it was

found a relationship between improvements

in lymphocyte subpopulations and both bio-

chemical and anthropometric variables.

Furthermore, in other studies, it has

been observed that monocytes, B cells, NK

cells, and T cells (CD4+ and CD8+) are

found in higher proportions in people with

obesity and provide a link between systemic

inflammation and IR

37-40

, which would guide

us to reiterate that having found some of

these cells decreased after physical activity

means an improvement of the inflamma-

tory process that is associated with IR and

metabolic alterations, representing a better

metabolic state for the participants.

On the other hand, in persons with

obesity, immunosenescent behavior has

been reported, similar to that appearing in

the elderly. This has been denominated as

“premature immunosenescence”, an imbal-

ance between senescent, naïve, and mem-

350 Rodríguez-López et al.

Investigación Clínica 64(3): 2023

ory cells that renders the individual with

obesity more susceptible to the disease

19,

. The specific increase in memory cells in

obese patients could somehow reflect what

some authors have pointed out about the

capacity for proliferation and activation of

memory cells, revealing the high degree of

chronic adaptive immune activation

41,42

which has been associated, as has already

been mentioned, with metabolic alterations

in these patients.

In this sense, it has been observed that

exercise may counteract immunosenescence

and its associated diseases by limiting the

accumulation of senescent T cells and re-

populating the blood with naïve T cells

mainly through promoting the expansion of

the naïve cell repertoire as a consequence of

the apoptosis of senescent T cells

44-47

, this

apoptotic process is thought to induce he-

matopoietic stem cells production in the

bloodstream, which may move to the thymus

and stimulate the development of naïve T

cells

. In the present study, in addition to

finding an increase in naïve cells after train-

ing (TCD3+ (p<0.05) in persons with OW),

a correlation between such an increase and

the reduction of total lymphocytes, IR and

LDL- cholesterol was observed. These results

suggest that this training could promote

immunometabolic regulation in these pa-

tients. Furthermore, it has been found that

senescent T lymphocytes are related to high

percentages of body fat

44, 46, 48

. It would be

valuable and interesting to investigate the

presence of senescent T cells in persons with

obesity.

Strengths, limitations and conclusions

Exercise is one of the therapies that ac-

company the treatment of obesity; However,

on some occasions, depending on the period

and the routine that is studied, it has been

observed that “there is no change”, but with

this work, we can realize that the physical

activity (modified HIIT with moderate inten-

sity, in this case) carried out, is influencing

the inflammatory process that triggers obe-

sity and, in turn, these changes were related

to immunometabolic improvements, thus

highlighting the relevance of this study.

Some of the study’s strengths were that

it was possible to implement an exercise

routine in a sedentary population; immu-

nometabolic changes were obtained in only

eight weeks of exercise. Also, the presence of

comorbidities (for example, dyslipidemias,

hypertriglyceridemias, hyperglycemia, MS,

among others) was detected and treated in

25% of the participants with exercise; All in-

ternational standards were followed to evalu-

ate the selected variables.

Certain limitations of the present study

were: The lack of analysis of other inflamma-

tion markers that could give us more infor-

mation about the inflammatory process be-

fore and after routine physical activity and

the voluntary desertion of some patients due

to the problem of adherence to a routine in

sedentary people.

In conclusion, this study reports that

an eight-week modified HIIT program

brought about positive changes in peripher-

al lymphocyte subpopulations in sedentary

individuals with OW or Ob, as it observed

a reduction in TL and TCD8+ and an in-

crease in naïve cells, bringing the values

closer to those in persons with NW. These

changes correlated with healthier meta-

bolic variables. Also, differential leukocyte

changes were observed according to BMI.

These results represent novel knowledge

about the positive effects of HIIT, not only

regulating whole-body metabolism but also

regulating immunomodulatory effects with

anti-inflammatory benefits. All these re-

sults reinforce the benefits of HIIT as an ex-

ercise strategy to promote the regulation of

immunometabolism.

As shown in this study, exercising is es-

sential, and obese patients should be made

aware that they should make changes in their

lifestyle in general, particularly in terms of

having a more active life. For this reason, it

is essential to continue conducting studies

of this nature.

High-Intensity Interval Training improves immunometabolism in sedentary obesity 351

Vol. 64(3): 338 - 354, 2023

ACKNOWLEDGMENTS

The authors acknowledge LN María

Magdalena Rodríguez-Magallanes for techni-

cal support, as well as the National Council

of Science and Technology (CONACYT, Méxi-

co) for a postgraduate studies scholarship

awarded to Carmen Paulina Rodríguez-López

(371434).

Funding

None

Conflict of interest

None

ORCID numbers

• Carmen Paulina Rodríguez-López

(CPRL): 0000-0001-8226-4971

• María Cristina González- Torres

(MCGT): 0000-0002-3778-422X

• Oralia Nájera-Medina (ONM):

0000-0003-2166-3770

Authors contribution

CPRL: research design, perform the in-

terventions and experiments, data analysis,

interpretation of the results, preparation,

and writing of the article, elaboration of fig-

ures and tables.

ONM: research design, data analysis, in-

terpretation of the results, preparation, and

writing of the article.

MCGT: interpretations of the results,

preparation, and writing of the article.

All authors approved the final version of

the article for publication.

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