AACE MENA 2025-Breaking the Cycle: From Fat Cells and Gut to the Mind in Weight Regain

Video Transcription

Video Summary

The speaker discusses the challenges of long-term obesity and type 2 diabetes management, emphasizing weight regain after initial successful weight loss. Key studies, like the DiRECT trial, showed that intense dietary interventions can induce diabetes remission with significant weight loss; however, most participants regain weight over 5 years, leading to the return of symptoms and medication needs. This pattern is common across many studies.<br /><br />The talk explores the physiological mechanisms controlling body weight, highlighting it as a tightly regulated homeostatic system centered in the brain, especially the hypothalamus. Hormones such as leptin (from fat cells), ghrelin (hunger hormone), PYY (satiety hormone), and GLP-1 play crucial roles in signaling hunger and fullness. Despite weight loss reducing leptin and satiety hormones and increasing hunger signals, these hormonal changes promote weight regain by increasing appetite and reducing energy expenditure. The speaker notes that while leptin replacement works dramatically in rare leptin-deficient cases, it is ineffective for most obesity due to resistance.<br /><br />GLP-1-based therapies show promise by reducing appetite via hypothalamic and brain reward centers. However, clinical attempts to predict treatment success based on hormone levels have so far been inconclusive. Overall, obesity treatment faces biological resistance to sustained weight loss, necessitating multifaceted approaches that consider the complex hormonal and neurological control of appetite and metabolism.

Keywords

obesity management

type 2 diabetes

weight regain

DiRECT trial

hormonal regulation

leptin resistance

GLP-1 therapies