Lipolysis of white adipose tissue triacylglycerol stores results in the liberation of glycerol and nonesterified fatty acids that are released into the vasculature for use by other organs as energy substrates. In response to changes in nutritional state, lipolysis rates are precisely regulated through hormonal and biochemical signals. These signals modulate the activity of lipolytic enzymes and accessory proteins, allowing for maximal responsiveness of adipose tissue to changes in energy requirements and availability. Recently, a number of novel adipocyte triacylglyceride lipases have been identified, including desnutrin/ATGL, greatly expanding our understanding of adipocyte lipolysis. We have also begun to better appreciate the role of a number of nonenzymatic proteins that are critical to triacylglyceride breakdown. This review provides an overview of key mediators of lipolysis and the regulation of this process by changes in nutritional status and nutrient intakes.
We have used rat cDNA microarrays to identify adipocyte-specific genes that could play an important role in adipocyte differentiation or function. Here, we report the cloning and identification of a 2.0-kb mRNA coding for a putative protein that we have designated as desnutrin. The novel gene is expressed predominantly in adipose tissue, and its expression is induced early during 3T3-L1 adipocyte differentiation. Desnutrin mRNA levels were regulated by the nutritional status of animals, being transiently induced during fasting. In vitro desnutrin gene expression was up-regulated by dexamethasone in a dose-dependent manner but not by cAMP, suggesting that glucocorticoids could mediate the increase in desnutrin mRNA levels observed during fasting. Desnutrin mRNA codes for a 486-amino acid putative protein containing a patatin-like domain, characteristic of many plant acyl hydrolases belonging to the patatin family. Confocal microscopy of enhanced green fluorescent protein-tagged desnutrin protein-transfected cells showed that the fusion protein localized in the cytoplasm. Moreover, cells overexpressing desnutrin by transfection showed an increase in triglyceride hydrolysis. Interestingly, we also found that the desnutrin gene expression level was lower in ob/ob and db/db obese mouse models. Overall, our data suggest that the newly identified desnutrin gene codes for an adipocyte protein that may function as a lipase and play a role in the adaptive response to a low energy state, such as fasting, by providing fatty acids to other tissues for oxidation. In addition, decreased expression of desnutrin in obesity models suggests its possible contribution to the pathophysiology of obesity.Triglycerides serve as the most efficient form of energy storage in times of caloric excess in many organisms. During periods of energy demand, triglycerides can be rapidly mobilized by the hydrolytic action of lipases, releasing free fatty acids that are oxidized to meet the energy requirement of the organism.
A main function of white adipose tissue is to release fatty acids from triacylglycerol for other tissues to use as an energy source. While endocrine regulation of lipolysis has been extensively studied, autocrine/paracrine regulation is not well understood. Here, we describe the role of AdPLA, the newly identified major adipocyte phospholipase A2, in the regulation of lipolysis and adiposity. AdPLA null mice have a markedly higher rate of lipolysis, due to increased cAMP levels arising from the marked reduction in adipose PGE2 that binds the Gαi-coupled receptor, EP3. AdPLA null mice have drastically reduced adipose tissue mass and triglyceride content, with normal adipogenesis. They also have higher energy expenditure with higher fatty acid oxidation within adipocytes. AdPLA deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and critical for the development of obesity.
Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the hydrolytic action of lipases, with the release of fatty acids (FA) that are used by other tissues during times of energy deprivation. Unlike synthesis of TAG, which occurs not only in adipose tissue but also in other tissues such as liver for very-low-density lipoprotein formation, hydrolysis of TAG, lipolysis, predominantly occurs in adipose tissue. Until recently, hormone-sensitive lipase was considered to be the key rate-limiting enzyme responsible for regulating TAG mobilization. However, recent studies on hormone-sensitive lipase-null mice have challenged such a concept. A novel lipase named desnutrin/ATGL has been recently discovered to play a key role in lipolysis in adipocytes. Lipolysis is under tight hormonal regulation. Although opposing regulation of lipolysis in adipose tissue by insulin and catecholamines is well understood, autocrine/paracrine factors may also participate in its regulation. Intricate cooperation of these endocrine and autocrine/paracrine factors leads to a fine regulation of lipolysis in adipocytes, needed for energy homeostasis. In this review, we summarize and discuss the recent progress made in the regulation of adipocyte lipolysis.
Background: Docosahexaenoic acid (DHA) and arachidonic acid (ARA) are major components of the cerebral cortex and visual system, where they play a critical role in neural development. We quantitatively mapped fatty acids in 26 regions of the four-week-old breastfed baboon CNS, and studied the influence of dietary DHA and ARA supplementation and prematurity on CNS DHA and ARA concentrations.
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