Lipoproteins in Drosophila melanogaster—Assembly, Function, and Influence on Tissue Lipid Composition

Palm, Wilhelm; Sampaio, Júlio L.; Brankatschk, Marko; Carvalho, Maria; Mahmoud, Ali; Shevchenko, Andrej; Eaton, Suzanne

doi:10.1371/journal.pgen.1002828

Cited by 241 publications

(404 citation statements)

References 64 publications

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“…In addition, overexpression of b-spectrin in the fat body led to abnormal accumulation of lipid droplets in the midgut epithelium. Similar phenotypes, affecting fat body and midgut lipid droplets, were described in studies of lipophorin knockdown in the fat body (Panakova et al 2005;Palm et al 2012). Lipophorin is the lipoprotein responsible for translocation of dietary fat from the midgut to the fat body during larval development (Arrese et al 2001;Canavoso et al 2001;Van Der Horst et al 2009;Van Der Horst and Rodenburg 2010).…”

supporting

confidence: 52%

“…Once loaded, it can circulate back to the fat body for unloading and recycling. Some of the associated cofactors required for loading and unloading of lipophorin are beginning to be elucidated (Palm et al 2012), but the picture at present is far from complete. There is evidence that lipophorin can be endocytosed by fat body cells (Dantuma et al 1998).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of lipophorin function leads to an abnormal accumulation of lipid droplets in the midgut epithelium (Panakova et al 2005;Palm et al 2012;this study). Significantly, no such accumulation occurred with loss of spectrin function, indicating that lipophorin continues to transport dietary lipid in the absence of cortical lipid droplets in the fat body.…”

Section: Implications For Redundant Functionmentioning

confidence: 94%

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Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

et al. 2013

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Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma membrane, cell polarity, and secretory membrane traffic. However, many of the underlying molecular mechanisms remain unexplained by prevailing models. Here we used the larval fat body of Drosophila melanogaster as a genetic model system to further elucidate mechanisms of ab-spectrin function. The results provide unexpected new insights into spectrin function as well as mechanisms of dietary fat uptake and storage. We show that loss of a-or b-spectrin in the fat body eliminated a population of small cortical lipid droplets and altered plasma membrane architecture, but did not affect viability of the organism. We present a novel model in which ab-spectrin directly couples lipid uptake at the plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong overexpression of b-spectrin caused fat body atrophy and larval lethality. Overexpression of b-spectrin also perturbed transport of dietary fat from the midgut to the fat body. This hypermorphic phenotype appears to be the result of blocking secretion of the lipid carrier lipophorin from fat cells. However, this midgut phenotype was never seen with spectrin loss of function, suggesting that spectrin is not normally required for lipophorin secretion or function. The b-spectrin hypermorphic phenotype was ameliorated by co-overexpression of a-spectrin. Based on the overexpression results here, we propose that b-spectrin family members may be prone to hypermorphic effects (including effects on secretion) if their activity is not properly regulated. MEMBERS of the spectrin and ankyrin gene families are ubiquitous in animal cells and defects in these genes are responsible for a range of inherited human disorders, including spinocerebellar ataxia type 5 (SCA5) (Ikeda et al. 2006), anemia (Lux andPalek 1995), and Duchenne muscular dystrophy (Koenig et al. 1988). In most cases, the precise molecular mechanisms underlying the disease process are incompletely understood. Spectrin and ankyrin are most familiar as components of a subplasma membrane protein scaffold known as the spectrin cytoskeleton (Baines 2010). In one long-standing hypothesis the spectrin cytoskeleton is thought to capture and stabilize interacting membrane proteins as they arrive at the cell surface, creating domains of specialized composition and function (Dubreuil 2006).Recent genetic studies in a number of model systems suggest that spectrin and ankyrin have further roles in intracellular membrane traffic (Kizhatil et al. 2007(Kizhatil et al. , 2009Ayalon et al. 2008;Stabach et al. 2008;Clarkson et al. 2010;Lorenzo et al. 2010;Tjota et al. 2011).Given the conservation of spectrin and ankyrin genes between vertebrates and invertebrates, one would expect that their functions should also be conserved. Indeed, as is the case in vertebrates, loss-of-function mutations of a-and b-spectrin and ankyrin2 in Drosophila are lethal early in development (Lee et al. 1993;Dubreuil et al. 2000;Koch et al. 2008;Pielag...

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supporting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Implications For Redundant Functionmentioning

confidence: 94%

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Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

et al. 2013

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“…This function is consistent with the IIS-dependent induction of lipophorin receptor 2 (LpR2) in oenocytes of fasting flies. Lipophorin functions as the main lipid transport protein in the hemolymph of both larvae and adults (44)(45)(46), and lipophorin receptor is involved in the uptake of neutral lipids in various tissues (44,47). Interestingly, inhibiting IIS activity in oenocytes is sufficient to cause metabolic imbalance in flies even under fed conditions (Fig.…”

Section: Iis Is Required In Oenocytes To Accumulate Lipid Droplets Dumentioning

confidence: 99%

Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes

Chatterjee

Katewa

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Metabolic adaptation to changing dietary conditions is critical to maintain homeostasis of the internal milieu. In metazoans, this adaptation is achieved by a combination of tissue-autonomous metabolic adjustments and endocrine signals that coordinate the mobilization, turnover, and storage of nutrients across tissues. To understand metabolic adaptation comprehensively, detailed insight into these tissue interactions is necessary. Here we characterize the tissue-specific response to fasting in adult flies and identify an endocrine interaction between the fat body and liverlike oenocytes that regulates the mobilization of lipid stores. Using tissue-specific expression profiling, we confirm that oenocytes in adult flies play a central role in the metabolic adaptation to fasting. Furthermore, we find that fat body-derived Drosophila insulinlike peptide 6 (dILP6) induces lipid uptake in oenocytes, promoting lipid turnover during fasting and increasing starvation tolerance of the animal. Selective activation of insulin/IGF signaling in oenocytes by a fat body-derived peptide represents a previously unidentified regulatory principle in the control of metabolic adaptation and starvation tolerance.T o maintain metabolic homeostasis during fasting periods, metazoans have to coordinate the mobilization of glycogen, lipids, and protein, ensuring an adequate energy supply across tissues. In addition to tissue-autonomous metabolic adjustments, endocrine signals are therefore critical components of the fasting response (1, 2). In mammals, the liver is central to adjusting intermediary metabolism during fasting. Starvation stimulates lipid accumulation in hepatocytes, which oxidize these lipids to provide energy in the form of ketone bodies for other tissues. Hepatocytes also respond to glucagon and insulin signals to control the expression of enzymes involved in glycogenolysis and gluconeogenesis, lipolysis, fatty acid oxidation, and ketogenesis, all regulated by a battery of transcription factors that include forkhead box O (Foxo), cAMP-response element binding (CREB), peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1a), and hepatocyte nuclear factor 4a (HNF4a) (3-5). At the same time, the liver integrates a suite of endocrine signals derived from major energy storing and consuming tissues, such as the brain, the adipose tissue, and the muscle (1). Deregulation of these processes can lead to hepatic steatosis and is a major cause of metabolic diseases, including diabetes and metabolic syndrome (1,3,6).Drosophila has emerged as a productive model organism in which to characterize the endocrine regulation of metabolic adaptation (7,8). The central function of the liver in metabolic adaptation of flies is shared by the fat body and oenocytes. Whereas the fat body is an important glycogen and fat storage organ in flies, it also serves as an endocrine organ to coordinate metabolic homeostasis (9-12). Oenocytes have a critical role in lipid mobilization and turnover in larvae, accumulating lipids during s...

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“…Although the insect lipophorin system can carry a range of lipids (including phospholipids), sterols and hydrocarbons, DAG is the primary circulating lipid destined for metabolic consumption in insects. Insect lipophorins are not restricted to shuttling lipids from FBCs to a consumer tissue: it is equally possible to acquire an ingested lipid at the gut and transport that directly to the metabolizing tissue or to the FBCs for storage Palm et al, 2012). DAGs bound to LDLp are hydrolysed into FFAs+glycerol at the surface of the recipient cell by a membranebound lipase, and the FFAs are transported into the cell and translocated to the mitochondrion via fatty acid binding proteins ( Fig.…”

Section: A Brief Overview Of Insect Lipid Metabolismmentioning

confidence: 99%

The many roles of fats in overwintering insects

Sinclair

Marshall

2018

Journal of Experimental Biology

119

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Temperate, polar and alpine insects generally do not feed over winter and hence must manage their energy stores to fuel their metabolism over winter and to meet the energetic demands of development and reproduction in the spring. In this Review, we give an overview of the accumulation, use and conservation of fat reserves in overwintering insects and discuss the ways insects modify fats to facilitate their selective consumption or conservation. Many insects are in diapause and have depressed metabolic rates over winter; together with low temperatures, this means that lipid stores are likely to be consumed predominantly in the autumn and spring, when temperatures are higher but insects remain dormant. Although there is ample evidence for a shift towards less-saturated lipids in overwintering insects, switches between the use of carbohydrate and lipid stores during winter have not been well-explored. Insects usually accumulate cryoprotectants over winter, and the resulting increase in haemolymph viscosity is likely to reduce lipid transport. For freezetolerant insects (which withstand internal ice), we speculate that impaired oxygen delivery limits lipid oxidation when frozen. Acetylated triacylglycerols remain liquid at low temperatures and interact with water molecules, providing intriguing possibilities for a role in cryoprotection. Similarly, antifreeze glycolipids may play an important role in structuring water and ice during overwintering. We also touch on the uncertain role of non-esterified fatty acids in insect overwintering. In conclusion, lipids are an important component of insect overwintering energetics, but there remain many uncertainties ripe for detailed exploration.

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Lipoproteins in Drosophila melanogaster—Assembly, Function, and Influence on Tissue Lipid Composition

Cited by 241 publications

References 64 publications

Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

Genetic Studies of Spectrin in the Larval Fat Body ofDrosophila melanogaster: Evidence for a Novel Lipid Uptake Apparatus

Control of metabolic adaptation to fasting by dILP6-induced insulin signaling in Drosophila oenocytes

The many roles of fats in overwintering insects

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