Exercise Effects on Cardiometabolic Health and Sestrin-2 in Hypertensive Obese Women (SES-EX)

Effects of Moderate-Intensity Continuous Exercise Versus Brisk Interval Exercise on Cardiometabolic Parameters and Sestrin-2 Levels in Hypertensive Obese Women: A Randomized Controlled Trial

Obesity is a chronic and complex disease characterized by excessive fat accumulation that adversely affects health and quality of life. It is commonly accompanied by low-grade chronic systemic inflammation, which contributes to the development of insulin resistance, type 2 diabetes, dyslipidemia, hypertension, and cardiovascular diseases. Hypertension is highly prevalent among individuals with obesity, and excess body weight is a major contributor to elevated blood pressure and related cardiometabolic risk.

Regular aerobic exercise is a cornerstone of non-pharmacological management for both obesity and hypertension and has been shown to reduce chronic inflammation by downregulating pro-inflammatory pathways and upregulating anti-inflammatory mechanisms. Sestrin-2, a stress-responsive protein encoded by the SESN2 gene, has been proposed as an important regulator of metabolic homeostasis and inflammation through activation of the AMPK pathway and inhibition of NF-κB signaling. However, evidence regarding the effects of different exercise modalities on circulating Sestrin-2 levels in hypertensive obese individuals remains limited.

This prospective, randomized controlled trial aims to compare the effects of two different aerobic exercise protocols on serum Sestrin-2 levels, inflammatory status, and cardiometabolic parameters in hypertensive obese women. Cardiopulmonary exercise testing will be used to comprehensively assess cardiorespiratory fitness and physiological responses to exercise. The results of this study are expected to contribute to a better understanding of exercise-induced anti-inflammatory mechanisms and to support the development of safe, effective, and applicable exercise prescriptions for hypertensive obese women.

Study Overview

• Status: Not yet recruiting
• Conditions: Hypertension; Obesity
• Intervention / Treatment: Behavioral: Moderate-Intensity Continuous Exercise; Behavioral: Brisk Interval Exercise

Detailed Description

Obesity is a chronic disease associated with excessive adipose tissue accumulation and a persistent low-grade inflammatory state, which contributes to the development of cardiometabolic disorders such as hypertension, insulin resistance, dyslipidemia, and cardiovascular disease. In women, the coexistence of obesity and hypertension substantially increases morbidity and negatively affects functional capacity and quality of life. Exercise training is a cornerstone of lifestyle-based management; however, the optimal characteristics of aerobic exercise prescription and its effects on emerging molecular biomarkers remain incompletely understood.

Sestrin-2 is a stress-inducible protein encoded by the SESN2 gene and has been implicated in metabolic regulation through activation of the AMP-activated protein kinase pathway and suppression of inflammatory signaling pathways, including nuclear factor kappa B. Experimental and clinical evidence suggests that Sestrin-2 may play a protective role against obesity-related inflammation and metabolic dysfunction. Nevertheless, data regarding the modulation of circulating Sestrin-2 levels in response to different aerobic exercise modalities in hypertensive obese women are limited.

This study is designed as a prospective, randomized controlled trial including hypertensive obese women who meet predefined eligibility criteria. Participants are randomly allocated to one of two supervised aerobic exercise intervention groups: moderate-intensity continuous exercise or brisk interval exercise. Both interventions are conducted for a predefined training period under standardized conditions.

Cardiopulmonary exercise testing is performed to assess cardiorespiratory fitness and physiological responses to exercise, including maximal oxygen consumption. Blood samples are collected to measure serum Sestrin-2 levels and cardiometabolic parameters. Additional assessments include lipid profile, indices of insulin resistance, anthropometric measurements, functional capacity evaluated by the six-minute walk test, and patient-reported questionnaire outcomes.

The primary outcome measures of the study are changes in serum Sestrin-2 levels and maximal oxygen consumption. Secondary outcome measures include changes in cardiometabolic risk factors, functional capacity, and anthropometric parameters. The findings of this study are expected to provide insight into exercise-induced anti-inflammatory mechanisms and to inform evidence-based aerobic exercise prescriptions for hypertensive obese women.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rukiye AKAY, MD; Phone Number: +905392333789; Email: rukiye.akay@sbu.edu.tr

Study Locations

• Turkey (Türkiye)
  • Kayseri
    • Kayseri, Kayseri, Turkey (Türkiye)
      • Kayseri City Hospital
      • Contact: Rukiye Akay, MD; Phone Number: 05392333789; Email: rukiye.akay@sbu.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female participants aged between 30 and 65 years
• Body mass index between 30.0 and <40.0 kg/m² (Class I and Class II obesity)
• Diagnosis of hypertension according to the 2018 European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines
• Sedentary lifestyle, defined as total weekly exercise duration of less than 60 minutes
• Medically eligible for exercise participation, with approval from a Physical Medicine and Rehabilitation specialist and an Internal Medicine specialist
• Willingness to participate in the study and provision of written informed consent

Exclusion Criteria:

• Neuromuscular disorders, uncontrolled psychiatric diseases, or cognitive impairment limiting exercise participation
• Congestive heart failure, unstable angina, or acute cardiac conditions including acute myocardial infarction, acute endocarditis, myocarditis, or pericarditis
• Presence of uncontrolled systemic diseases, including:
• Uncontrolled hypertension
• Uncontrolled diabetes mellitus
• Chronic liver failure
• Chronic kidney disease or patients receiving dialysis
• Chronic obstructive pulmonary disease or asthma
• History or presence of malignancy
• Acute infection at the time of enrollment
• Acute peripheral vascular disease
• Symptomatic severe aortic stenosis
• Acute pulmonary embolism or pulmonary infarction
• Use of systemic corticosteroids or immunosuppressive medications
• Inability to comply with the study protocol or lack of cooperation
• Refusal to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate-Intensity Continuous Exercise; Participants perform supervised moderate-intensity continuous aerobic exercise at a prescribed intensity and frequency.	Behavioral: Moderate-Intensity Continuous Exercise; Supervised moderate-intensity continuous aerobic exercise performed at a prescribed intensity and frequency for the duration of the intervention period.
Experimental: Brisk Interval Exercise; Participants perform supervised interval aerobic exercise consisting of alternating bouts of higher and moderate intensity.	Behavioral: Brisk Interval Exercise; Supervised interval aerobic exercise consisting of alternating bouts of higher and moderate intensity performed throughout the intervention period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Sestrin-2 Level	Serum Sestrin-2 levels will be measured using enzyme-linked immunosorbent assay (ELISA). Blood samples will be collected 48 hours before the start of the 8-week exercise program and 48 hours after completion of the intervention in order to avoid the acute effects of exercise. The primary outcome is the change in Sestrin-2 levels from baseline to post-intervention.	Baseline and end of 8-week intervention
Maximal Oxygen Consumption (VO2max)	VO2max will be assessed using cardiopulmonary exercise testing (CPET) according to standardized protocols. Measurements will be performed before the start of the exercise program and after completion of the 8-week intervention. The change in VO2max from baseline to post-intervention will be analyzed.	Baseline and end of 8-week intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Profile	Fasting blood samples will be collected to assess lipid profile parameters, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. Standard laboratory methods will be used for biochemical analysis. Changes in lipid profile parameters from baseline to the end of the 8-week exercise intervention will be evaluated.	Baseline and end of 8-week intervention
Insulin Resistance	Insulin resistance will be assessed using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Fasting plasma glucose and fasting insulin levels will be measured using standard laboratory methods, and HOMA-IR will be calculated accordingly. The change in HOMA-IR from baseline to the end of the 8-week exercise intervention will be analyzed.	Baseline and end of 8-week intervention
Functional Capacity	Functional exercise capacity will be assessed using the 6-minute walk test (6MWT) according to established guidelines. The total distance walked in six minutes will be recorded at baseline and after completion of the 8-week exercise intervention. The change in 6-minute walk distance from baseline to post-intervention will be analyzed.	Baseline and end of 8-week intervention
Blood Pressure	Resting systolic and diastolic blood pressure will be measured using a validated automated sphygmomanometer according to standardized guidelines. Measurements will be performed after at least 5 minutes of seated rest at baseline and after completion of the 8-week exercise intervention. The change in systolic and diastolic blood pressure from baseline to post-intervention will be analyzed.	Baseline and end of 8-week intervention
Change in body weight	Body weight will be measured in kilograms using a calibrated digital scale at baseline and after completion of the 8-week exercise intervention. The change in body weight from baseline to post-intervention will be analyzed.	Baseline and Week 8
Change in body mass index (BMI)	Body mass index (BMI) will be calculated as weight in kilograms divided by height in meters squared (kg/m²). BMI will be assessed at baseline and after completion of the 8-week exercise intervention. The change in BMI from baseline to post-intervention will be analyzed.	Baseline and Week 8
Change in waist circumference	Waist circumference will be measured in centimeters using a non-elastic measuring tape according to standardized procedures. Measurements will be performed at baseline and after completion of the 8-week exercise intervention. The change in waist circumference from baseline to post-intervention will be analyzed.	Baseline and Week 8
Change in International Physical Activity Questionnaire (IPAQ) score	Physical activity levels will be assessed using the International Physical Activity Questionnaire (IPAQ). The IPAQ provides physical activity estimates expressed as metabolic equivalent task minutes per week (MET-min/week), with higher values indicating higher physical activity levels. The questionnaire will be administered at baseline and after completion of the 8-week exercise intervention. The change in IPAQ score from baseline to post-intervention will be analyzed.	Baseline and Week 8
Change in Hospital Anxiety and Depression Scale (HADS) scores	Anxiety and depressive symptoms will be assessed using the Hospital Anxiety and Depression Scale (HADS). The HADS consists of 14 items and includes two subscales: anxiety (HADS-A) and depression (HADS-D), each scored from 0 to 21. Higher scores indicate greater levels of anxiety or depressive symptoms. The questionnaire will be administered at baseline and after completion of the 8-week exercise intervention. Changes in HADS-A and HADS-D scores from baseline to post-intervention will be analyzed.	Baseline and Week 8

Collaborators and Investigators

• Sponsor: Havva Talay Çalış

Publications and helpful links

General Publications

• Lee JH, Budanov AV, Karin M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metabolism. 2013;18(6):792-801.
• Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018;39(33):3021-3104.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 4, 2026
• First Submitted That Met QC Criteria: January 17, 2026
• First Posted (Actual): January 27, 2026

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 17, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Hypertension; obesity; Aerobic Exercise; VO2max; Cardiopulmonary Exercise Testing; Sestrin-2
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Hypertension
• Other Study ID Numbers: KayseriCHsestrin2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No