Lipophagy: A New Perspective of Natural Products in Type 2 Diabetes Mellitus Treatment

Abstract

Autophagy has been reported to involve in the pathogenesis of type 2 diabetes mellitus (T2DM), which protects the insulin target tissues and pancreatic β-cells. However, autophagy is inhibited when the cells are lipid overload. That, in turn, increases the accumulation of fat. Lipotoxicity caused by excessive lipid accumulation contributes to pathogenesis of T2DM. Therefore, it is undeniable to break the vicious circles between lipid excess and autophagy deficiency. Lipophagy, a selective form of autophagy, is characterized by selective breakdown of lipid droplets (LDs). The nutritional status of cells contributes to the way of autophagy (selective or non-selective), while selective autophagy helps to accurately remove excess substances. It seems that lipophagy could be an effective means to decrease abnormal lipid accumulation that leads to insulin resistance and β-cell impairment by removing ectopic LDs. Based on this process, many natural compounds have been reported to decrease lipid accumulation in tissues through autophagy-lysosomal pathway, which gradually highlights the significance of lipophagy. In this review, we focus on the mechanisms that lipophagy improves T2DM and natural products that are applied to induce lipophagy. It is also suggested that natural herbs with rich contents of natural products inducing lipophagy would be potential candidates for alleviating T2DM.

The role of autophagy in insulin resistance and glucolipid metabolism and potential use of autophagy modulating natural products in the treatment of type 2 diabetes mellitus

“…Recent studies have shed light on the potential of mitophagy and lipophagy in the treatment of T2DM. 181,182 Metformin, a widely used oral T2DM drug, 183 has been found to improve mitochondrial morphology and function by upregulating mitophagy. 183 This beneficial effect contributes to enhancing β-cell function and preventing the aggravation of hyperglycemia in T2DM patients.…”

“…184 Lipophagy, on the other hand, targets lipid droplets and reduces excessive fat accumulation, leading to the alleviation of IR. 182 Natural products like berberine and ginsenoside Rb2 have shown their ability to stimulate both autophagy and lipophagy, thereby reducing abnormal hepatic lipidation and improving IR in animal models of T2DM. 185,186 Therefore, the distinction between different forms of autophagy, such as mitophagy and lipophagy, offers an avenue for novel approaches in combating T2DM.…”

“…This beneficial effect contributes to enhancing β ‐cell function and preventing the aggravation of hyperglycemia in T2DM patients 184 . Lipophagy, on the other hand, targets lipid droplets and reduces excessive fat accumulation, leading to the alleviation of IR 182 . Natural products like berberine and ginsenoside Rb2 have shown their ability to stimulate both autophagy and lipophagy, thereby reducing abnormal hepatic lipidation and improving IR in animal models of T2DM 185,186 .…”

“…Recent studies have shed light on the potential of mitophagy and lipophagy in the treatment of T2DM 181,182 . Metformin, a widely used oral T2DM drug, 183 has been found to improve mitochondrial morphology and function by upregulating mitophagy 183 .…”

Crosstalk between autophagy and insulin resistance: evidence from different tissues

“…Additionally, the production of VLDL and apoB100 was excessive in those with insulin resistance [ 151 ]. Following the inhibition of autophagy by genetic and/or pharmacological factors, aberrant fat accumulation occurs in the liver, leading to insulin resistance [ 152 ]. The absence of lipophagy in the liver cells blocks the hydrolysis of TGs into FFAs and leads to steatosis and insulin resistance [ 53 ].…”