Effects of an Energy-restricted Diet on the Expression of the Sirtuin-1 and Leptin Receptor Genes in White Blood Cells, and Cardiometabolic Markers in Individuals With Hypertriglyceridemia: Comparison Between Low and High Weight Loss Responders

Hypertriglyceridemia (HTG), defined as fasting triglycerides (TGs) ≥150 mg/dL, is a prevalent condition in the adult population, with an increasing prevalence that parallels the rise in obesity rates. There is a robust body of literature indicating a correlation between mild to moderate HTG and a number of complications, including cardiovascular disease and pancreatitis.

Lifestyle changes and weight loss could improve HTG. Dietary calorie restriction is a cornerstone in the weight loss program. However, the rate of achieving substantial weight loss through dietary interventions is often not high. Consequently, identifying factors associated with responders to both desirable and undesirable weight loss before initiating dietary interventions can help individuals struggling with weight loss. In this context, gene expression markers have been proposed as promising tools. For instance, a number of studies have identified predictors of body weight and improvement in glycemic status by comparing the transcriptomic profile of adipose tissue from obese and overweight individuals during a low-calorie diet. In other studies, peripheral blood cells have been utilized for the examination of gene expression profiles. Peripheral blood cells, including white blood cells, are readily available and, express most of the human genome. Consequently, they can reflect the gene expression of key tissues affecting energy homeostasis in response to nutritional changes or weight change. Sirtuin-1 (SIRT1) gene expression, a known regulator of glucose and lipid homeostasis, is altered by caloric restriction and weight loss. It is possible that the basal level of SIRT-1 expression may predict the metabolic response to weight loss. Conversely, leptin exerts influence over several physiological processes, including communication with the central nervous system, energy expenditure, and food intake. Obese individuals may exhibit higher levels of leptin resistance and reduced access to the central nervous system via the blood-brain barrier in comparison to lean individuals. The extent of leptin receptor expression may serve as a determining factor in these disparities. Consequently, the level of leptin receptor expression may also influence the response of individuals to a weight loss program.

The present study aims to evaluate the expression of SIRT-1 and leptin receptor genes in white blood cells and changes in cardiometabolic factors in individuals with hypertriglyceridemia associated with overweight and obesity. The variables will be compared at the beginning and end of the study between those who have lost less weight after two months and those who have lost more weight. The relationship of these variables to the percentage of weight loss will also be examined. The primary hypothesis posited that specific pre-weight loss factors could predict optimal weight loss responders. Secondary hypotheses were formulated with the objective of investigating how cardiometabolic markers would be affected by weight loss in response to a hypocaloric diet in subjects with HTG.

Methods:

The study population consists of people with mild to moderate hypertriglyceridemia who are overweight or obese and are placed on a low-calorie diet program.