Latest trends on interplay of autophagy, adipose tissue, and gut microbiota in obesity-related metabolic disorders

This review aims to synthesize current research on the intricate relationships among visceral obesity (VO), autophagy (Atg), gut microbiota, and adipose tissue dysfunction, all of which contribute significantly to insulin resistance (IR) and associated metabolic disorders. Specifically, it seeks to identify key mechanistic pathways and potential therapeutic targets. Contemporary investigations have established VO as a principal etiological factor in diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD), accounting for a substantial proportion of global metabolic disease incidence. Notable discoveries include: (1) the nuanced role of Atg in adipose tissue homeostasis, wherein tissue-specific aberrations, such as diminished ATG5 expression in visceral adipose tissue, exacerbate IR. Conversely, pharmacologically induced Atg, exemplified by rapamycin administration, enhances insulin sensitivity by 15–25 % in rodent models. (2) Alterations in gut microbial composition, characterized by a 40 % decrease in Bacteroidetes and an increase in Firmicutes, correlate with elevated visceral adiposity and systemic inflammation. Fecal microbiota transplantation in human studies has demonstrated restoration of microbial diversity, resulting in a 12 % reduction in hepatic steatosis in NAFLD patients; (3) adipose tissue macrophages exhibit a pro-inflammatory phenotype, evidenced by a 2-3-fold elevation in TNF-α levels in VO, which precipitates metabolic dysfunction through Toll-like receptor 4 and nuclear factor kappa B signaling pathways. The interactive network involving Atg, gut microbiota, and adipose tissue represents a pivotal axis in the development of metabolic diseases. While interventions targeting Atg and microbiota modulation demonstrate potential, inconsistent outcomes, such as the variable efficacy of probiotic therapies, underscore the context-dependent nature of these mechanisms. Existing therapeutic approaches, including lifestyle modifications, pharmacological interventions, and bariatric surgery, address adiposity but require more targeted approaches. Future research should prioritize elucidating tissue-specific Atg regulation and developing personalized microbiota-based therapies to manage the complex pathophysiology of obesity-related disorders effectively. • The Interplay of Autophagy, Adipose Tissue, and Gut Microbiota in Obesity-Related Metabolic Disorders were reviewed. • Lifestyle management, drug therapy, and bariatric surgery have emerged to treat the entire body fat well. • Obesity-related metabolic diseases highlight the need for comprehensive mechanical research. • Research is required to understand the underlying pathways and to develop targeted interventions.