Healthy vs Unhealthy Obesity: Mehanistic Insights and Effects of Time-Restricted Eating

Obesity-related cardiometabolic diseases are now a leading cause of death worldwide. These diseases result from a dysfunctional adipose tissue (AT) that induces inflammation, insulin resistance and altered endocrine function. However, not all obese people develop metabolic complications, which has given rise to the concept of "metabolically healthy obesity" (MHO). Recent evidence suggests that intermittent fasting methods, in particular time-restricted eating (TRE) may be effective in improving cardiometabolic health, independently of weight loss, and this could be particularly effective in MUO subjects. The investigators hypothesize that in young male adults TRE is a more effective/beneficial approach in MUO than in MHO due to the weight loss-independent improvement in their inflammatory and metabolic derangements. To this aim, a 16-week 8h TRE intervention study will be performed in MHO and MUO subjects, assessing anthropometric, endocrine, and other outcomes.

Although clinical differences between metabolically healthy and unhealthy obesity (MHO and MUO, respectively) have been extensively described, cellular mechanisms involved in these different phenotypes are largely unknown. This evidence is crucial for proposing preventive and therapeutic approaches. Recently, intermittent fasting methods, in particular time-restricted eating (TRE, a self-selected daily limited eating window protocol), have shown to be effective in improving cardiometabolic health, independently of weight loss, which could be particularly relevant in MUO. The investigators will recruit young (20-22y-old) males with obesity (Body Mass Index≥30) and classify them as MHO or MUO (≤1 or ≥3 metabolic syndrome risk factors, respectively). A 16-week, 8h TRE intervention will be conducted in MHO vs. MUO subgroups, to assess and compare the anthropometric, metabolic, endocrine, inflammatory and peripheral blood mononuclear cell (PBMC) mechanistic/signaling response. The investigators expect to advance the understanding of cellular mechanisms implicated in MHO and MUO, including potential therapeutic targets. Ultimately, the investigators expect to find relevant opportunities for intervention to prevent the serious cardiometabolic consequences of obesity.