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Autophagy and Regulation of Lipid Metabolism

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Sensory and Metabolic Control of Energy Balance

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 52))

Abstract

Macroautophagy (henceforth referred to as autophagy) is an in-bulk lysosomal degradative pathway that plays a crucial role in the maintenance of cellular homeostasis through the removal of damaged proteins and aged organelles. Following nutrient deprivation, a primary cellular response is the induction of autophagy that breaks down redundant cellular components and provides amino acids and additional precursor molecules for processes critical for cellular survival. In parallel, nutrient depletion leads to the mobilization of cellular lipid stores to supply free fatty acids for energy, thus pointing to regulatory and functional similarities between autophagy and lipid metabolism. The current chapter discusses the novel and mutually exclusive roles of autophagy in the regulation of lipid metabolism in the liver and of fat storage within the adipose tissue. Our studies in cultured hepatocytes and the murine liver have demonstrated that autophagy serves to degrade intracellular lipid stores through a process that we have termed “macrolipophagy” and that ablation of liver-specific autophagy leads to excessive hepatic lipid accumulation and the development of fatty liver. In contrast, preadipocytes in culture that lacked autophagy failed to differentiate into mature adipocytes and exhibited a reduction in fat storage that translated to decreased adipose tissue mass in an in vivo mouse model. These recent findings establish an association between autophagy and regulation of hepatic lipid metabolism and adipose tissue biology, thus providing new mechanistic insights into the regulation of these complex processes. These findings also highlight the possibility of novel therapeutic approaches, such as differential organ-specific regulation of autophagy to solve problems that arise from lipid over accumulation that occur in the metabolic syndrome and with aging.

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Acknowledgments

This work was supported by National Institutes of Health grants from the National Institute of Diabetes and Digestive and Kidney Diseases to Dr. Ana Maria Cuervo (AMC) and Dr. Mark Czaja and from the National Institute of Aging and a Glenn Award to AMC; RS is supported by a NIH NIDDK K01 (DK087776-01) grant. The author thanks Dr. Ana Maria Cuervo for thought-provoking discussions and Dr. Susmita Kaushik for the critical reading of this manuscript.

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Correspondence to Rajat Singh .

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Singh, R. (2011). Autophagy and Regulation of Lipid Metabolism. In: Meyerhof, W., Beisiegel, U., Joost, HG. (eds) Sensory and Metabolic Control of Energy Balance. Results and Problems in Cell Differentiation, vol 52. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14426-4_4

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