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Trends in Cell Biology Apr 2023Adipose tissue signals to brain, liver, and muscles to control whole body metabolism through secreted lipid and protein factors as well as neurotransmission, but the... (Review)
Review
Adipose tissue signals to brain, liver, and muscles to control whole body metabolism through secreted lipid and protein factors as well as neurotransmission, but the mechanisms involved are incompletely understood. Adipocytes sequester triglyceride (TG) in fed conditions stimulated by insulin, while in fasting catecholamines trigger TG hydrolysis, releasing glycerol and fatty acids (FAs). These antagonistic hormone actions result in part from insulin's ability to inhibit cAMP levels generated through such G-protein-coupled receptors as catecholamine-activated β-adrenergic receptors. Consistent with these antagonistic signaling modes, acute actions of catecholamines cause insulin resistance. Yet, paradoxically, chronically activating adipocytes by catecholamines cause increased glucose tolerance, as does insulin. Recent results have helped to unravel this conundrum by revealing enhanced complexities of these hormones' signaling networks, including identification of unexpected common signaling nodes between these canonically antagonistic hormones.
Topics: Humans; Adipocytes; Adipose Tissue; Catecholamines; Insulin; Lipolysis; Cyclic AMP
PubMed: 35989245
DOI: 10.1016/j.tcb.2022.07.009 -
PloS One 2016Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of...
Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.
Topics: 3T3-L1 Cells; Adipocytes; Animals; Blotting, Western; Cell Count; Cell Differentiation; Escherichia coli; Fibronectins; Gene Expression Regulation; Glucose; Humans; Lipolysis; Mice; Real-Time Polymerase Chain Reaction; Recombinant Proteins
PubMed: 26799325
DOI: 10.1371/journal.pone.0147480 -
Cell Metabolism Nov 2017We thought we knew how the heat-producing uncoupling protein 1 in brown adipose tissue was activated: by fatty acids released upon lipid droplet breakdown in the brown...
We thought we knew how the heat-producing uncoupling protein 1 in brown adipose tissue was activated: by fatty acids released upon lipid droplet breakdown in the brown adipocytes. However, two studies in this issue (Schreiber et al., 2017; Shin et al., 2017) imply that this classical model may not be valid: heat can be produced in brown fat without intracellular lipolysis.
Topics: Adipose Tissue, Brown; Ion Channels; Lipolysis; Mitochondrial Proteins; Myocardium; Thermogenesis; Uncoupling Protein 1
PubMed: 29117542
DOI: 10.1016/j.cmet.2017.10.012 -
Science Advances Sep 2022The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy...
The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked β-d--acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue-specific innervation.
Topics: Adipose Tissue; Animals; Body Weight; Hypothalamus; Lipolysis; Mice; N-Acetylglucosaminyltransferases; Obesity
PubMed: 36044565
DOI: 10.1126/sciadv.abn8092 -
EMBO Reports Nov 2020Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological...
Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl-1 and lid-1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell-autonomous regulation of neural functions and neurodegeneration.
Topics: Animals; Fatty Acids, Unsaturated; Lipid Droplets; Lipid Metabolism; Lipolysis; Neurons; Triglycerides
PubMed: 33034119
DOI: 10.15252/embr.202050214 -
Current Atherosclerosis Reports Nov 2013The endothelium is often viewed solely as the barrier that prevents the penetration of circulating lipoproteins into the arterial wall. However, recent research has... (Review)
Review
The endothelium is often viewed solely as the barrier that prevents the penetration of circulating lipoproteins into the arterial wall. However, recent research has demonstrated that the endothelium has an important part in regulating circulating fatty acids and lipoproteins, and is in turn affected by these lipids/lipoproteins in ways that appear to have important repercussions for atherosclerosis. Thus, a number of potentially toxic lipids are produced during lipolysis of lipoproteins at the endothelial cell surface. Catabolism of triglyceride-rich lipoproteins creates free fatty acids that are readily taken up by endothelial cells, and, likely through the action of acyl-CoA synthetases, exacerbate inflammatory processes. In this article, we review how the endothelium participates in lipoprotein metabolism, how lipids alter endothelial functions, and how lipids are internalized, processed, and transported into the subendothelial space. Finally, we address the many endothelial changes that might promote atherogenesis, especially in the setting of diabetes.
Topics: Animals; Endothelium, Vascular; Fatty Acids; Humans; Lipid Metabolism; Lipids; Lipolysis; Lipoproteins; Triglycerides
PubMed: 24037142
DOI: 10.1007/s11883-013-0365-1 -
Drug Delivery and Translational Research May 2023Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key...
Lipid-based formulations (LBFs) are used by the pharmaceutical industry in oral delivery systems for both poorly water-soluble drugs and biologics. Digestibility is key for the performance of LBFs and in vitro lipolysis is commonly used to compare the digestibility of LBFs. Results from in vitro lipolysis experiments depend highly on the experimental conditions and formulation characteristics, such as droplet size (which defines the surface area available for digestion) and interfacial structure. This study introduced the intrinsic lipolysis rate (ILR) as a surface area-independent approach to compare lipid digestibility. Pure acylglycerol nanoemulsions, stabilized with polysorbate 80 at low concentration, were formulated and digested according to a standardized pH-stat lipolysis protocol. A methodology originally developed to calculate the intrinsic dissolution rate of poorly water-soluble drugs was adapted for the rapid calculation of ILR from lipolysis data. The impact of surfactant concentration on the apparent lipolysis rate and lipid structure on ILR was systematically investigated. The surfactant polysorbate 80 inhibited lipolysis of tricaprylin nanoemulsions in a concentration-dependent manner. Coarse-grained molecular dynamics simulations supported these experimental observations. In the absence of bile and phospholipids, tricaprylin was shielded from lipase at 0.25% polysorbate 80. In contrast, the inclusion of bile salt and phospholipid increased the surfactant-free area and improved the colloidal presentation of the lipids to the enzyme, especially at 0.125% polysorbate 80. At a constant and low surfactant content, acylglycerol digestibility increased with decreasing acyl chain length, decreased esterification, and increasing unsaturation. The calculated ILR of pure acylglycerols was successfully used to accurately predict the IRL of binary lipid mixtures. The ILR measurements hold great promise as an efficient method supporting pharmaceutical formulation scientists in the design of LBFs with specific digestion profiles.
Topics: Lipids; Lipolysis; Polysorbates; Glycerides; Pharmaceutical Preparations; Surface-Active Agents; Water; Solubility
PubMed: 36209313
DOI: 10.1007/s13346-022-01246-y -
Obesity (Silver Spring, Md.) Oct 2015To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss.
OBJECTIVE
To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss.
METHODS
High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were studied following a massive weight loss by diet and Roux-en-Y gastric bypass (RYGB).
RESULTS
The mitochondrial respiratory rates were similar in OB and T2DM, and the mass-specific oxygen flux increased significantly 4 and 18 months post-surgery (P < 0.05). With normalization to mitochondrial content, no differences in oxidative capacity after RYGB were seen. The ratio between the oxidative phosphorylation system capacity (P) and the capacity of the electron transfer system (E) increased 18 months after RYGB in both groups (P < 0.05). Lipolysis per fat mass was similar in the two groups and was increased (P < 0.05) and lipid oxidation during hyperinsulinemia decreased 4 months post-surgery. In T2DM, visceral fat mass was always higher relative to the body fat mass (%) compared to OB.
CONCLUSIONS
Adipose tissue mitochondrial respiratory capacity increases with RYGB. Adipocytes adapt to massive weight loss by increasing the phosphorylation system ratio (P/E), suggesting an increased ability to oxidize substrates after RYGB. Lipolysis increases in the short term post-surgery, and insulin sensitivity for suppression of lipolysis increases with RYGB.
Topics: Adipose Tissue; Adolescent; Adult; DNA, Mitochondrial; Diabetes Mellitus, Type 2; Diet; Female; Gastric Bypass; Humans; Insulin Resistance; Lipolysis; Longitudinal Studies; Male; Middle Aged; Obesity; Weight Loss; Young Adult
PubMed: 26337597
DOI: 10.1002/oby.21223 -
Journal of Lipid Research Feb 1994Fatty acids are important oxidative fuel for liver, kidney, skeletal muscle, and myocardium. There has been much interest in the role of fatty acids in the pathogenesis... (Review)
Review
Fatty acids are important oxidative fuel for liver, kidney, skeletal muscle, and myocardium. There has been much interest in the role of fatty acids in the pathogenesis of non-insulin-dependent diabetes because they compete with glucose for oxygen and inhibit whole body glucose disposal via the 'Randle cycle,' Control of lipolysis in adipose tissue determines systemic fatty acid supply. A wide range of hormones and other substances have been recognized as regulators of lipolysis, but insulin and catecholamines appear to be the most important. The regulation of lipolysis, in most circumstances, provides a supply of lipid fuel exceeding the rate of lipid oxidation, requiring reesterification to triglyceride of surplus circulating free fatty acids. Thus, free fatty acid supply is usually not matched to the demand for lipid oxidation, and there is no known mechanism for accurately sensing such demand. This lax regulation may be disadvantageous in conditions such as aging, stress, obesity, and diabetes, where the antilipolytic effect of insulin is impaired and lipolysis is therefore increased. In these conditions, the surfeit of fatty acid may impair glucoregulation. In addition, the excess lipolysis may induce hypertriglyceridemia (via increased very low density lipoprotein production) and thus contribute to atherogenesis. Considerable additional research is needed in order to fully understand both normal lipolytic regulation and the abnormalities of lipolysis which accompany pathological conditions.
Topics: Adipose Tissue; Diabetes Mellitus; Fatty Acids; Humans; Lipolysis; Liver; Muscles; Obesity
PubMed: 8169522
DOI: No ID Found -
International Journal of Molecular... Jan 2022Hydrogen sulfide (HS) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the...
Hydrogen sulfide (HS) and inorganic polysulfides are important signaling molecules; however, little is known about their role in the adipose tissue. We examined the effect of HS and polysulfides on adipose tissue lipolysis. HS and polysulfide production by mesenteric adipose tissue explants in rats was measured. The effect of NaS and NaS, the HS and polysulfide donors, respectively, on lipolysis markers, plasma non-esterified fatty acids (NEFA) and glycerol, was examined. NaS but not NaS increased plasma NEFA and glycerol in a time- and dose-dependent manner. NaS increased cyclic AMP but not cyclic GMP concentration in the adipose tissue. The effect of NaS on NEFA and glycerol was abolished by the specific inhibitor of protein kinase A, KT5720. The effect of NaS on lipolysis was not abolished by propranolol, suggesting no involvement of β-adrenergic receptors. In addition, NaS had no effect on phosphodiesterase activity in the adipose tissue. Obesity induced by feeding rats a highly palatable diet for 1 month was associated with increased plasma NEFA and glycerol concentrations, as well as greater HS production in the adipose tissue. In conclusion, HS stimulates lipolysis and may contribute to the enhanced lipolysis associated with obesity.
Topics: Adipose Tissue; Animals; Cyclic GMP; Fatty Acids, Nonesterified; Hydrogen Sulfide; Lipolysis; Male; Metabolic Syndrome; Obesity; Rats; Rats, Wistar; Receptors, Adrenergic, beta; Sulfides
PubMed: 35163277
DOI: 10.3390/ijms23031346