Obesity is a chronic, multifactorial disease and a major global public health challenge. Defined by excessive fat accumulation, obesity significantly increases the risk of numerous diseases, including type 2 diabetes mellitus (T2DM), cardiovascular disease, heart failure, and metabolic dysfunction-associated steatotic liver disease, contributing to rising morbidity and mortality rates worldwide. Although several pharmacological treatments have demonstrated notable efficacy in weight management, concerns regarding drug safety remain a significant challenge. Metabolic bariatric surgery (MBS) has emerged as the most effective intervention for achieving long-term and sustained weight loss; however, it is typically reserved for advanced stages of the disease. Moreover, the role of MBS in managing obesity-related comorbidities remains a topic of ongoing debate. In this review, we provide a comprehensive analysis of the epidemiology of obesity and its associated comorbidities, along with the latest insights into the mechanisms underlying obesity-induced chronic complications. Growing evidence highlights the crucial role of imbalances between white and brown adipose tissues, alterations in gut microbiota, genetic and epigenetic modifications, and immune system dysregulation in driving obesity and its related conditions. These emerging insights have unveiled numerous potential therapeutic targets with promising weight-reducing effects. Furthermore, advancements in our understanding of signal transduction pathways may pave the way for future multimodal therapeutic strategies in obesity management, ushering in a new era of precision medicine.

Simple obesity is a worldwide epidemic associated with rapidly growing morbidity and mortality which imposes an enormous burden on individual and public health. As a part of Traditional Chinese Medicine (TCM), acupuncture has shown the positive efficacy in the management of simple obesity. In this article, we comprehensively review the clinical and animal studies that demonstrated the potential mechanisms of acupuncture treatment for simple obesity. Clinical studies suggested that acupuncture regulates endocrine system, promotes digestion, attenuates oxidative stress, and modulates relevant molecules of metabolism in patients of simple obesity. Evidence from laboratory indicated that acupuncture regulates lipid metabolism, modulates inflammatory responses, and promotes white adipose tissue browning. Acupuncture also suppresses appetite through regulating appetite regulatory hormones and the downstream signaling pathway. The evidence from clinical and animal studies indicates that acupuncture induces multifaceted regulation through complex mechanisms and moreover a single factor may not be enough to explain the beneficial effects against simple obesity.

Acupuncture has been widely used for obesity treatment, but its mechanism is still unclear. To investigate the molecular mechanisms, we applied electroacupuncture (EA) at the Zusanli (ST36) acupoint and treadmill exercise (TE) in a diet‐induced obese (DIO) rat model and used RNA sequencing (RNA‐seq) to identify molecular consequences. Forty Sprague‐Dawley male rats were selected and randomly divided into five groups: control (C), DIO model (M), EA, TE, and EA + TE groups. According to the results, acupuncture reduced body weight and the ratio of retroperitoneal white adipose tissue (retro‐WAT) to body weight. Total RNA was extracted from the retro‐WAT from five groups for RNA‐seq. Differentially expressed genes (DEG) analysis showed that there were obvious differences among the four comparisons of C vs. M, M vs. EA, M vs. TE, and M vs. EA + TE, followed by 1383, 913, 3324, and 2794 DE genes. Gene ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to further classify the DEGs. Several GO terms were commonly significantly enriched in both M vs. TE and M vs. EA, such as myofibril and muscle contraction. In addition, some pathways were regulated by EA and TE, such as the peroxisome proliferator activated receptor signaling pathway and calcium signaling pathway. This study is the first to compare and analyze the differences in gene expression profiles in the retro‐WAT of rats in different groups, which provide a clue for further investigation into the molecular mechanisms of obesity treatment by EA and TE.