Exercise Effects on Cardiometabolic Health and Sestrin-2 in Hypertensive Obese Women

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.

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.

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