Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications - PubMed (original) (raw)

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Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications

Mark J Czaja. Am J Physiol Cell Physiol. 2010 May.

Abstract

Autophagy is a lysosomal degradative pathway critical for the removal and breakdown of cellular components such as organelles and proteins. Despite striking similarities in the regulation and function of autophagy and lipid metabolism, the two processes have only recently been shown to be interrelated. This review details new findings of critical functions for autophagy in lipid metabolism and storage. Studies in hepatocytes and liver have demonstrated that macroautophagy mediates the breakdown of lipids stored in lipid droplets and that an inhibition of autophagy leads to the development of a fatty liver. In contrast, in adipocytes the loss of macroautophagy decreases the amount of lipid stored in adipose tissue through effects on white and brown adipocyte differentiation. Other investigations have indicated that the relationship between autophagy and lipids is bidirectional, with changes in cellular lipid content altering autophagic function. These newly described links between autophagy and lipid metabolism and storage have provided new insights into the mechanisms of both processes. The findings also suggest possible new therapeutic approaches to the problems of lipid overaccumulation and impaired autophagy that occur with aging and the metabolic syndrome.

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Figures

Fig. 1.

Fig. 1.

Function of macroautophagy in hepatocyte lipid metabolism. Small lipid droplets in the hepatocyte are engulfed whole either by themselves or in combination with other substrates such as mitochondria in autophagosomes. Portions of larger lipid droplets are removed and also sequestered in autophagosomes. Autophagosomes fuse with lysosomes for cargo degradation. Breakdown of triglycerides in lipid droplets by lysosomal lipases yields free fatty acids (FFA) which can undergo β-oxidation in mitochondria to supply the hepatocyte with ATP. Macroautophagy therefore performs a critical function in the regulation of liver lipid stores.

Fig. 2.

Fig. 2.

Macroautophagy in adipocytes regulates cellular differentiation. Inhibition of macroautophagy reduces white adipose tissue (WAT) mass and increases the amount of brown adipose tissue (BAT). This effect may be mediated through an inhibitory effect on white adipocyte stem cells or a stimulatory effect on brown adipocyte progenitor cells. Alternatively, the loss of autophagy may alter white/brown adipocyte transdifferentiation to favor brown adipocyte differentiation. The loss of WAT mass together with an augmented rate of fatty acid β-oxidation resulting from the increase in brown adipocytes leads to decreased lipid storage and a reduction in fat mass. This decrease in fat has the beneficial effects of reducing body weight and improving insulin sensitivity.

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