Autophagy can be generally divided into non
Autophagy can be generally divided into non-selective bulk autophagy and selective autophagy. Non-selective autophagy breaks down proteins and organelles to provide the cell with nutrients in response to starvation. Selective autophagy removes damaged and excess organelles as well as protein sphingosine 1-phosphate receptor modulator using specific receptors in both nutrient-sufficient and -poor conditions as well as other pathophysiological conditions, such as exposure to xenobiotics or drugs.
Adipose tissue: white, brown, and beige WAT can be further categorized as subcutaneous WAT and visceral WAT, which differ in origin and distribution. It is believed that visceral WAT plays a more important role in metabolic regulation. White adipocytes are characterized by a single large LD, and the nucleus and cytoplasm are squeezed into a thin rim at the periphery. While the primary function of WAT is to store energy, WAT also has other important functions, such as acting as a hormone receptor in response to insulin, growth hormones, norepinephrine, and glucocorticoids. Moreover, WAT acts as a thermal insulator that helps maintain body temperature and an endocrine organ that secretes adipokines, such as resistin, adiponectin, leptin, and apelin. When nutrient intake is sufficient, the insulin receptor on WAT is activated by insulin released from the pancreas, which leads to a dephosphorylation cascade and inactivation of hormone-sensitive lipase (HSL), favoring storage of triglycerides (TGs) in LDs. When the body needs energy, the stored TGs are broken down to fatty acids (FAs), which are taken up by muscle and cardiac tissue as a fuel source, and glycerol, which is taken up by the liver for gluconeogenesis. Obesity and overweight are usually accompanied by increased white adipocyte size and number. BAT cells are characterized by numerous smaller LDs, considerable cytoplasm, a large number of mitochondria that give the tissue its characteristic brown color, and plentiful capillaries in the tissue. BAT dissipates LDs and generates body heat via uncoupling protein 1 (UCP1). Additionally, it is abundant in newborns and hibernating mammals. Interestingly, another category of adipocytes, named beige or brite (brown-in-white) adipocytes, has been recently described and has garnered increasing research interest. Though they are located in WAT and share the same origin as white adipocytes, beige adipocytes are more similar to brown adipocytes in terms of multilocular LDs, abundant mitochondrial content, and increased UCP1 gene expression, which is essential for thermogenic capacity. Beige adipocytes can be induced by cold and β-adrenergic agonists. Stimulation of beige adipocyte activity may offset dysregulated WAT and improve metabolic disease status. There is also emerging research interest in the interconversion between white and brown adipocytes. Besides adipocytes, there are other adipose tissue cell types that contribute to its growth and function, including preadipocytes, macrophages, lymphocytes, fibroblasts, and vascular cells. Preadipocytes, also known as adipose progenitor cells, are important for controlling adipocyte number, especially in the context of obesity and diabetes. Increased macrophages in fat tissue contribute to systemic inflammation and insulin resistance.
Autophagy in adipose biology Autophagy has been implicated in regulating adipose tissue mass, differentiation, and physiological functions. Altered adipose tissue autophagy levels are associated with metabolic dysregulation, such as obesity. An adipocyte-specific autophagy-deficient mouse model exhibits impaired adipogenesis and decreased susceptibility to high fat diet-induced obesity. While it is still debatable, it is generally thought that autophagy in adipose tissue may help to remove damaged proteins to relieve ER stress or to remove damaged mitochondria to prevent adipocyte cell death, which may be beneficial for reducing adipose tissue inflammation. In contrast, as discussed above, mice with genetic adipocyte-specific deletion of either Atg5 or Atg7 display decreased weight gain, increased insulin sensitivity, and browning of white adipocytes, supporting a beneficial role for the lack of autophagy in adipocytes against metabolic dysfunction. However, it should be noted that these adipocyte-specific Atg5 or Atg7 knockout mice display autophagy defects early in development. It is highly likely that autophagy in fully matured adipocytes has different effects. Additional future studies are required to dissect the exact role of autophagy in adipocyte biology. Using inducible systems to delete the genes encoding Atg proteins in adult mouse adipocytes or using lipophilic inhibitors that can accumulate in the adipose tissue to specifically block autophagy in mature adipocytes will be very helpful.