Unlocking the secrets: Adipose tissue dysfunction and atherosclerosis-mechanisms and innovative therapeutic approaches

Abstract

In a healthy state, adipose tissue plays a crucial role in energy storage, hormone regulation, and metabolic processes. However, adipose tissue dysfunction can occur due to factors such as obesity, inflammation, or metabolic disorders. Adipose tissue dysfunction has been identified as a pivotal factor in the development of atherosclerosis, linking metabolic disturbances with chronic vascular inflammation. This review explores how adipose tissue dysfunction and atherosclerosis, highlighting its endocrine, inflammatory, and metabolic functions. The dysregulation of adipokine secretion, persistent low-grade inflammation, and compromised lipid metabolism collectively contribute to vascular injury and the progression of atherosclerosis. The distinct functions of white, brown, beige, and perivascular adipose tissues in both healthy and diseased are examined. Dysfunction in white adipose tissue, characterized by abnormal expansion, inflammation, and ectopic lipid accumulation, significantly contributes to systemic insulin resistance and atherogenic dyslipidemia. Additionally, dysfunctional brown and beige adipose tissues exacerbate these conditions by impairing thermogenesis and lipid clearance. In obesity, Perivascular adipose tissue (PVAT) shifts from an anti-inflammatory to a pro-inflammatory state in obesity, which directly contributes to endothelial dysfunction and vascular remodeling. The review highlights recent advancements in understanding mitochondrial dysfunction in adipocytes and its wider implications for energy metabolism and inflammation. The review also evaluates novel therapeutic strategies to address adipose tissue dysfunction, including SGLT2 inhibitors, PPARγ agonists, and innovative approaches such as PVAT modulation and therapies that promote adipose browning. By integrating mechanistic insights with translational approaches, this review highlights the essential role of adipose tissue in atherosclerosis and identifies potential therapeutic targets for the prevention and management of cardiovascular diseases (CVDs) Figure 1.

Keywords: Adipokines; Adipose tissue browning; Adipose tissue dysfunction; And vascular inflammation; Atherosclerosis; Beige adipose tissue (BeAT); Cardiometabolic diseases; Chronic inflammation; Endothelial dysfunction; Lipid metabolism; PPARγ agonists; Perivascular adipose tissue (PVAT); White adipose tissue (WAT); brown adipose tissue (BAT).