Weight Gain and Adipose Tissue

This study aims to examine the role of weight gain in adipose tissue immune cell influx and development of obesity related cardiometabolic disorders. Adipose tissue-mediated chronic systemic inflammation is implicated in the development of cardiometabolic disorders in obesity. Therefore, resolution of adipose tissue inflammation may be key to ameliorating obesity-associated dyslipidemia, insulin-resistance, and cardiovascular disease. Proinflammatory cytokines contribute to the initial influx of immune cells into adipose tissue during weight gain. However, mechanisms regulating these cytokines in the adipose tissue milieu and the effects of weight gain on adipose tissue are not completely understood. The study proposes to investigate the molecular events contributing to increased infiltration of macrophages and T-cells into adipose tissue during weight gain. The central hypothesis is that in lean subjects (with low body fat mass), healthy fat gain which is associated with decreased expression of proinflammatory cytokines. However, in obesity (high body fat mass), adipose tissue is altered, which permits increased expression of inflammatory cytokines and further fat gain results in influx of immune cells. To test the hypothesis, adipose tissue from well characterized lean (control, with low body fat) and obese individuals (with high body fat) at baseline and after a modest 5% weight gain will be used. Adipose tissue samples after subsequent weight loss will also be examined. For this study, obesity will be defined by body composition rather than body mass index (BMI), as several studies have shown that BMI does not adequately define obesity and several individuals with normal BMI may indeed have high body fat mass. Individuals with body fat content ≤25% for men, & <35% for women) will be considered lean and individuals with body fat content >25% for men, ≥35% for women will be considered obese.

Lean individuals are defined as having body fat content less or equal to 25% in men and less than 35% for women. Overfeeding induced weight gain and subsequent weight loss

obese individuals are defined as having body fat content more than 25% in men and more than 35% for women. Overfeeding induced weight gain and subsequent weight loss

Change from baseline in adipose tissue inflammation by 8 week of modest weight gain followed by 8 week of weight loss.

Adipose tissue inflammation will be measures by RTPCR and Western Blot. These will be presented as ratio to endogenous house keeping gene.

Change from baseline in blood pressure by 8 week of modest weight gain followed by 8 weeks of weight loss.

Inclusion Criteria Age: 18 to 40 (inclusive) years BMI 18.5 <30 kg/m2 Gender: Both males and females will be allowed to participate in the study Predominantly sedentary Absence of any chronic medical conditions other than seasonal or environmental allergies On no prescription medications other than second generation antihistamines (cetirizine , Fexofenadine, Desloratadine, Loratadine, etc), oral contraceptive pills, or intrauterine devices Not a current smoker or tobacco user Not pregnant or breast feeding and not intending to become pregnant or breast feed Lean (low body fat mass) (body fat content ≤ 25% for men, < 35% for women) n=7; Obese (high body fat mass) (body fat content >25% for men, ≥ 35% for women) n=7 Ability to provide written informed consent Exclusion Criteria Vulnerable study population will be excluded Presence of chronic diseases such as diabetes, and cardiovascular disease Pregnancy Anemic (hemoglobin <13.5 g/dL for men and <12.0 g/dL for women) Postmenopausal Smoking Use of chronic Medications (aspirin, statin, anti-inflammatory drugs) Subjects found to have significant sleep disorders will be excluded Dietary restrictions including lactose intolerance, and vegan diet Eating disorders that may interfere with weight gain and weight loss