scholarly journals Advanced lipodystrophy reverses fatty liver in mice lacking adipocyte hormone-sensitive lipase

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laura Pajed ◽  
Ulrike Taschler ◽  
Anna Tilp ◽  
Peter Hofer ◽  
Petra Kotzbeck ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
De Novo ◽  
Lipolytic Activity ◽  
De Novo Lipogenesis ◽  
Hormone Sensitive Lipase ◽  
Hepatic Lipid Accumulation ◽  
Hormone Sensitive

AbstractModulation of adipocyte lipolysis represents an attractive approach to treat metabolic diseases. Lipolysis mainly depends on two enzymes: adipose triglyceride lipase and hormone-sensitive lipase (HSL). Here, we investigated the short- and long-term impact of adipocyte HSL on energy homeostasis using adipocyte-specific HSL knockout (AHKO) mice. AHKO mice fed high-fat-diet (HFD) progressively developed lipodystrophy accompanied by excessive hepatic lipid accumulation. The increased hepatic triglyceride deposition was due to induced de novo lipogenesis driven by increased fatty acid release from adipose tissue during refeeding related to defective insulin signaling in adipose tissue. Remarkably, the fatty liver of HFD-fed AHKO mice reversed with advanced age. The reversal of fatty liver coincided with a pronounced lipodystrophic phenotype leading to blunted lipolytic activity in adipose tissue. Overall, we demonstrate that impaired adipocyte HSL-mediated lipolysis affects systemic energy homeostasis in AHKO mice, whereby with older age, these mice reverse their fatty liver despite advanced lipodystrophy.

scholarly journals Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states

2010 ◽  
Vol 299 (3) ◽  
pp. R728-R739 ◽  
Author(s):  
Barbara E. Hasek ◽  
Laura K. Stewart ◽  
Tara M. Henagan ◽  
Anik Boudreau ◽  
Natalie R. Lenard ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Uncoupling Protein ◽  
Nutrient Sensing ◽  
De Novo Lipogenesis ◽  
Endocrine Function ◽  
Fischer 344 ◽  
Methionine Restriction ◽  
Heat Increment

Dietary methionine restriction (MR) is a mimetic of chronic dietary restriction (DR) in the sense that MR increases rodent longevity, but without food restriction. We report here that MR also persistently increases total energy expenditure (EE) and limits fat deposition despite increasing weight-specific food consumption. In Fischer 344 (F344) rats consuming control or MR diets for 3, 9, and 20 mo, mean EE was 1.5-fold higher in MR vs. control rats, primarily due to higher EE during the night at all ages. The day-to-night transition produced a twofold higher heat increment of feeding (3.0°C vs. 1.5°C) in MR vs. controls and an exaggerated increase in respiratory quotient (RQ) to values greater than 1, indicative of the interconversion of glucose to lipid by de novo lipogenesis. The simultaneous inhibition of glucose utilization and shift to fat oxidation during the day was also more complete in MR (RQ ∼0.75) vs. controls (RQ ∼0.85). Dietary MR produced a rapid and persistent increase in uncoupling protein 1 expression in brown (BAT) and white adipose tissue (WAT) in conjunction with decreased leptin and increased adiponectin levels in serum, suggesting that remodeling of the metabolic and endocrine function of adipose tissue may have an important role in the overall increase in EE. We conclude that the hyperphagic response to dietary MR is matched to a coordinated increase in uncoupled respiration, suggesting the engagement of a nutrient-sensing mechanism, which compensates for limited methionine through integrated effects on energy homeostasis.

scholarly journals Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11630-11635 ◽  
Author(s):  
Yan Wang ◽  
Markey C. McNutt ◽  
Serena Banfi ◽  
Michael G. Levin ◽  
William L. Holland ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
De Novo ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
De Novo Lipogenesis ◽  
Fed State ◽  
Beneficial Effects ◽  
Brown Adipose

Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target.

scholarly journals The presence and role of hormone-sensitive lipase in heart muscle

1989 ◽  
Vol 258 (1) ◽  
pp. 67-72 ◽  
Author(s):  
C A Small ◽  
A J Garton ◽  
S J Yeaman
Keyword(s):  
Adipose Tissue ◽  
Heart Muscle ◽  
Lipolytic Activity ◽  
Hormone Sensitive Lipase ◽  
Energy Store ◽  
Dependent Protein ◽  
Hormone Sensitive ◽  
Rat Myocytes ◽  
Adipose Tissue Lipolysis

Hormone-sensitive lipase (HSL) catalyses the initial, rate-limiting, reaction in adipose-tissue lipolysis. Hormone-stimulated lipolytic activity has also been observed in the heart, where endogenous triacylglycerol is the major energy store. However, the identity of the intracellular lipase responsible has yet to be established. We have partially purified a neutral lipase from bovine heart muscle and compared its properties with those of HSL from bovine adipose tissue. The heart lipase has the same subunit Mr as HSL, is immunoprecipitated by antiserum raised against purified HSL and is phosphorylated by cyclic AMP-dependent protein kinase, apparently at the same site as HSL (as judged by h.p.l.c. of tryptic phosphopeptides). Phosphorylation of the heart lipase was found to result in increased enzyme activity, demonstrating the lipase's potential to respond to hormonal stimuli. The heart lipase was shown to be present in myocytes by its immunoprecipitation from homogenates of rat myocytes by anti-HSL antiserum. These findings are consistent with the conclusion that HSL is responsible for intracellular lipolysis in heart.

scholarly journals Transcriptomic Analysis of Gonadal Adipose Tissue in Male Mice Exposed Perinatally to 2,2′,4,4′-Tetrabromodiphenyl Ether (BDE-47)

2018 ◽  
Author(s):  
Aser Abrha ◽  
Alexander Suvorov
Keyword(s):  
Adipose Tissue ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Metabolic Diseases ◽  
De Novo ◽  
Coagulation Factors ◽  
Bioinformatic Analysis ◽  
De Novo Lipogenesis ◽  
Target Tissue ◽  
Pregnant Mice

For the majority of lipophilic compounds adipose tissue is traditionally considered as storage depot and only rarely as a target organ. Meanwhile, abnormalities in adipose tissue physiology induced by chemical exposures may contribute to the current epidemic of obesity and metabolic diseases. Polybrominated diphenyl ethers (PBDEs) is a group of lipophilic flame retardants found in majority of human samples in North America. Their ability to alter physiology of adipose tissue is unknown. We exposed pregnant mice to 0.2 mg/kg body weight/day of BDE-47 perinatally. Transcriptomic changes in gonadal adipose tissue were analyzed in male offspring using RNA-seq approach with subsequent bioinformatic analysis. Genes of coagulation and complement cascade, de novo lipogenesis, and xenobiotic metabolism were altered in expression in response to BDE-47 exposure. The affected molecular network included the following hubs: PPARα, HNF1A and HNF4. These findings suggest that adipose tissue should be considered a target tissue for BDE-47, in addition to its role as a storage depot. This study also builds a background for a targeted search of sensitive phenotypic endpoints of BDE-47 exposure, including lipid profile parameters and coagulation factors in circulation. Additional studies are needed to investigate the role of PBDEs as an obesogen.

scholarly journals Regulation of Triglyceride Metabolism.IV. Hormonal regulation of lipolysis in adipose tissue

2007 ◽  
Vol 293 (1) ◽  
pp. G1-G4 ◽  
Author(s):  
Kathy Jaworski ◽  
Eszter Sarkadi-Nagy ◽  
Robin E. Duncan ◽  
Maryam Ahmadian ◽  
Hei Sook Sul
Keyword(s):  
Adipose Tissue ◽  
Hormonal Regulation ◽  
Energy Homeostasis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Paracrine Factors ◽  
Fine Regulation ◽  
Hormone Sensitive ◽  
Energy Deprivation

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.

scholarly journals Emerging Roles for Serotonin in Regulating Metabolism: New Implications for an Ancient Molecule

2019 ◽  
Vol 40 (4) ◽  
pp. 1092-1107 ◽  
Author(s):  
Julian M Yabut ◽  
Justin D Crane ◽  
Alexander E Green ◽  
Damien J Keating ◽  
Waliul I Khan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Drug Targets ◽  
Energy Homeostasis ◽  
De Novo ◽  
Nutrient Absorption ◽  
The Body ◽  
De Novo Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Multiple Organs ◽  
Brown Adipose

Abstract Serotonin is a phylogenetically ancient biogenic amine that has played an integral role in maintaining energy homeostasis for billions of years. In mammals, serotonin produced within the central nervous system regulates behavior, suppresses appetite, and promotes energy expenditure by increasing sympathetic drive to brown adipose tissue. In addition to these central circuits, emerging evidence also suggests an important role for peripheral serotonin as a factor that enhances nutrient absorption and storage. Specifically, glucose and fatty acids stimulate the release of serotonin from the duodenum, promoting gut peristalsis and nutrient absorption. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue, while reducing lipolysis and the metabolic activity of brown and beige adipose tissue. Collectively, peripheral serotonin acts as an endocrine factor to promote the efficient storage of energy by upregulating lipid anabolism. Pharmacological inhibition of serotonin synthesis or signaling in key metabolic tissues are potential drug targets for obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

scholarly journals Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice

PLoS Genetics ◽  
2017 ◽  
Vol 13 (12) ◽  
pp. e1007110 ◽  
Author(s):  
Bo Xia ◽  
Guo He Cai ◽  
Hao Yang ◽  
Shu Pei Wang ◽  
Grant A. Mitchell ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Liver ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive
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