Insights by which TUDCA is a potential therapy against adiposity

Abstract

Adipose tissue is an organ with metabolic and endocrine activity. White, brown and ectopic adipose tissues have different structure, location, and function. Adipose tissue regulates energy homeostasis, providing energy in nutrient-deficient conditions and storing it in high-supply conditions. To attend to the high demand for energy storage during obesity, the adipose tissue undergoes morphological, functional and molecular changes. Endoplasmic reticulum (ER) stress has been evidenced as a molecular hallmark of metabolic disorders. In this sense, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), a bile acid conjugated to taurine with chemical chaperone activity, has emerged as a therapeutic strategy to minimize adipose tissue dysfunction and metabolic alterations associated with obesity. In this review, we highlight the effects of TUDCA and receptors TGR5 and FXR on adipose tissue in the setting of obesity. TUDCA has been demonstrated to limit metabolic disturbs associated to obesity by inhibiting ER stress, inflammation, and apoptosis in adipocytes. The beneficial effect of TUDCA on perivascular adipose tissue (PVAT) function and adiponectin release may be related to cardiovascular protection in obesity, although more studies are needed to clarify the mechanisms. Therefore, TUDCA has emerged as a potential therapeutic strategy for obesity and comorbidities.

Diabetes Mellitus, Energy Metabolism, and COVID-19

“…This causes lipid overflow to other organs, triggering a cascade of events that eventually results in increased gluconeogenesis and fasting glucose production, and ectopic fat accumulation leading to lipotoxicity and multiorgan insulin resistance ( 82 ). Mechanical stress on the adipocyte, release of damage-associated molecular proteins from dying adipocytes, activation of inflammatory signaling by free fatty acids (FFA) through the Toll-like receptor 4 or Toll-like receptor 2 on the adipocyte's plasma membrane, endoplasmic reticulum (ER), and oxidative stress also contribute to adipose tissue inflammation and insulin resistance ( 83-85 ). These early mechanisms contribute to the onset of a local inflammation that over time leads to spillover of pro-inflammatory cytokines and adipokines into the systemic circulation, worsening the multiorgan insulin resistance triggered by excess release of lipids from adipose tissue ( 82 ).…”