Browning of White Adipose Tissue as a Therapeutic Tool in the Fight against Atherosclerosis

Abstract

Despite continuous medical advances, atherosclerosis remains the prime cause of mortality worldwide. Emerging findings on brown and beige adipocytes highlighted that these fat cells share the specific ability of non-shivering thermogenesis due to the expression of uncoupling protein 1. Brown fat is established during embryogenesis, and beige cells emerge from white adipose tissue exposed to specific stimuli like cold exposure into a process called browning. The consecutive energy expenditure of both thermogenic adipose tissues has shown therapeutic potential in metabolic disorders like obesity and diabetes. The latest data suggest promising effects on atherosclerosis development as well. Upon cold exposure, mice and humans have a physiological increase in brown adipose tissue activation and browning of white adipocytes is promoted. The use of drugs like β3-adrenergic agonists in murine models induces similar effects. With respect to atheroprotection, thermogenic adipose tissue activation has beneficial outcomes in mice by decreasing plasma triglycerides, total cholesterol and low-density lipoproteins, by increasing high-density lipoproteins, and by inducing secretion of atheroprotective adipokines. Atheroprotective effects involve an unaffected hepatic clearance. Latest clinical data tend to find thinner atherosclerotic lesions in patients with higher brown adipose tissue activity. Strategies for preserving healthy arteries are a major concern for public health.

Pro-Inflammatory Profile of Adipokines in Obesity Contributes to Pathogenesis, Nutritional Disorders, and Cardiovascular Risk in Chronic Kidney Disease

“…BAT is rich in the mitochondrial protein—uncoupling protein 1 (UCP1), which dissipates energy in the form of heat and thus increases energy expenditure. Unlike WAT, BAT reduces hyperlipidemia and facilitates weight loss [ 16 , 17 ]. It is possible to induce UCP1 expression in white adipocytes, a process known as adipocyte browning.…”

“…The cells created in this way are beige adipocytes which, despite their different origins, have a similar structure and function to brown adipocytes. Browning of adipocytes induced by various factors, including exposure to cold, insulin, specific nutrients, or the presence of an excess of nutrients, has a positive effect on health [ 17 , 18 ].…”

“…Obesity is characterized by an increase in and dysregulation of WAT, especially visceral fat, which is associated with altered adipokine secretion. When the threshold of adipocyte storage capacity for fatty acids is exceeded, the processes of hypertrophy and hyperplasia take place [ 17 ]. An increased size of fat cells (hypertrophy) and their increased number (hyperplasia) differ in the way they affect the organism.…”

Global Adipose Tissue Remodeling During the First Month of Postnatal Life in Mice

“…The interconversion from white to beige adipocytes is a reversible, adaptive process ( 29 ), conferring varying degrees of non-shivering thermogenic capacity ( 30 , 31 ). Accordingly, beige adipocyte recruitment is intensely studied as putative pharmacological target process in the field of metabolic disease [reviewed in ( 32 )]. In iWAT, cold stimulation leads to a strong increase in the number of beige adipocytes ( 11 ).…”

On the Role of Paraoxonase-1 and Chemokine Ligand 2 (C-C motif) in Metabolic Alterations Linked to Inflammation and Disease. A 2021 Update

“…Atherosclerosis and cardiovascular diseases (CVD) are closely associated with obesity [128]. Perivascular inflammation plays a major role in the onset and development of atherosclerosis [129,130].…”