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Nutrients Jul 2023Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main...
Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main characteristic secondary metabolites of RCE are phytoecdysteroids. In order to determine an RCE's phytoecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of RCE and its secondary metabolites on adipogenesis and adipolysis. The evaluation of the anti-adipogenic and lipolytic effects was performed using human Simpson-Golabi-Behmel syndrome cells, where lipid staining and measurement of released glycerol and free fatty acids were employed. The HPTLC method confirmed the presence of 20-hydroxyecdysone (20E), ponasterone A (PA), and turkesterone (TU) in RCE. The observed results revealed that RCE, 20E, and TU significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Moreover, RCE and 20E were found to effectively stimulate basal lipolysis. However, no significant effects were observed with PA and TU applications. Based on our findings, RCE and 20E affect both lipogenesis and lipolysis, while TU only restrains adipogenesis. These results are fundamental for further investigations.
Topics: Humans; Mice; Animals; Adipogenesis; Leuzea; Plant Extracts; Lipid Metabolism; Lipolysis; Lipids; 3T3-L1 Cells
PubMed: 37447387
DOI: 10.3390/nu15133061 -
International Journal of Molecular... Apr 2022Oncostatin M (OSM) is an immune cell-derived cytokine that is upregulated in adipose tissue in obesity. Upon binding its receptor (OSMR), OSM induces the phosphorylation...
Oncostatin M (OSM) is an immune cell-derived cytokine that is upregulated in adipose tissue in obesity. Upon binding its receptor (OSMR), OSM induces the phosphorylation of the p66 subunit of Src homology 2 domain-containing transforming protein 1 (SHC1), called p66Shc, and activates the extracellular signal-related kinase (ERK) pathway. Mice with adipocyte-specific OSMR deletion () are insulin resistant and exhibit adipose tissue inflammation, suggesting that intact adipocyte OSM-OSMR signaling is necessary for maintaining adipose tissue health. How OSM affects specific adipocyte functions is still unclear. Here, we examined the effects of OSM on adipocyte lipolysis. We treated 3T3-L1 adipocytes with OSM, insulin, and/or inhibitors of SHC1 and ERK and measured glycerol release. We also measured phosphorylation of p66Shc, ERK, and insulin receptor substrate-1 (IRS1) and the expression of lipolysis-associated genes in OSM-exposed 3T3-L1 adipocytes and primary adipocytes from control and mice. We found that OSM induces adipocyte lipolysis via a p66Shc-ERK pathway and inhibits the suppression of lipolysis by insulin. Further, OSM induces phosphorylation of inhibitory IRS1 residues. We conclude that OSM is a stimulator of lipolysis and inhibits adipocyte insulin response. Future studies will determine how these roles of OSM affect adipose tissue function in health and disease.
Topics: 3T3-L1 Cells; Adipocytes; Animals; Extracellular Signal-Regulated MAP Kinases; Insulin; Insulin, Regular, Human; Lipolysis; Mice; Oncostatin M; Src Homology 2 Domain-Containing, Transforming Protein 1
PubMed: 35563078
DOI: 10.3390/ijms23094689 -
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 -
Molecular Metabolism Aug 2023Glucocorticoids are one of the most commonly prescribed classes of anti-inflammatory drugs; however, chronic treatment promotes iatrogenic (drug-induced) diabetes. As...
OBJECTIVE
Glucocorticoids are one of the most commonly prescribed classes of anti-inflammatory drugs; however, chronic treatment promotes iatrogenic (drug-induced) diabetes. As part of their physiological role, glucocorticoids stimulate lipolysis to spare glucose. We hypothesized that persistent stimulation of lipolysis during glucocorticoid therapy plays a causative role in the development of iatrogenic diabetes.
METHODS
Male C57BL/6J mice were given 100 μg/mL corticosterone (Cort) in the drinking water for two weeks and were fed either normal chow (TekLad 8640) or the same diet supplemented with an adipose triglyceride lipase inhibitor (Atglistatin - 2 g/kg diet) to inhibit the first step of lipolysis.
RESULTS
Herein, we report for the first time that glucocorticoid administration promotes a unique state of substrate excess and energetic overload in skeletal muscle that primarily results from the rampant mobilization of endogenous fuels. Inhibiting lipolysis protected mice from Cort-induced gains in fat mass, excess ectopic lipid accrual, hyperinsulinemia, and hyperglycemia. The role lipolysis plays in Cort-mediated pathology appears to differ between tissues. Within skeletal muscle, Cort-induced lipolysis facilitated diversion of glucose-derived carbons toward the pentose phosphate and hexosamine biosynthesis pathways but contributed to <3% of the Cort-induced genomic adaptations. In contrast, Cort stimulation of lipolysis accounted for ∼35% of the genomic changes in the liver but had minimal impact on hepatic metabolites reported.
CONCLUSIONS
These data support the idea that activation of lipolysis plays a causal role in the progression toward iatrogenic diabetes during glucocorticoid therapy with differential impact on skeletal muscle and liver.
Topics: Male; Mice; Animals; Glucocorticoids; Lipolysis; Insulin Resistance; Mice, Inbred C57BL; Corticosterone; Glucose; Iatrogenic Disease
PubMed: 37295745
DOI: 10.1016/j.molmet.2023.101751 -
Nature Microbiology Nov 2023Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for...
Trypanosoma brucei causes African trypanosomiasis, colonizing adipose tissue and inducing weight loss. Here we investigated the molecular mechanisms responsible for adipose mass loss and its impact on disease pathology. We found that lipolysis is activated early in infection. Mice lacking B and T lymphocytes fail to upregulate adipocyte lipolysis, resulting in higher fat mass retention. Genetic ablation of the rate-limiting adipose triglyceride lipase specifically from adipocytes (Adipoq-Atgl) prevented the stimulation of adipocyte lipolysis during infection, reducing fat mass loss. Surprisingly, these mice succumbed earlier and presented a higher parasite burden in the gonadal adipose tissue, indicating that host lipolysis limits parasite growth. Consistently, free fatty acids comparable with those of adipose interstitial fluid induced loss of parasite viability. Adipocyte lipolysis emerges as a mechanism controlling local parasite burden and affecting the loss of fat mass in African trypanosomiasis.
Topics: Animals; Mice; Lipolysis; Trypanosoma brucei brucei; Trypanosomiasis, African; Lipase; Adipocytes; Obesity
PubMed: 37828246
DOI: 10.1038/s41564-023-01496-7 -
Journal of Dairy Science Jan 2022Intense and protracted adipose tissue (AT) fat mobilization increases the risk of metabolic and inflammatory periparturient diseases in dairy cows. This vulnerability...
Intense and protracted adipose tissue (AT) fat mobilization increases the risk of metabolic and inflammatory periparturient diseases in dairy cows. This vulnerability increases when cows have endotoxemia-common during periparturient diseases such as mastitis, metritis, and pneumonia-but the mechanisms are unknown. Fat mobilization intensity is determined by the balance between lipolysis and lipogenesis. Around parturition, the rate of lipolysis surpasses that of lipogenesis, leading to enhanced free fatty acid release into the circulation. We hypothesized that exposure to endotoxin (ET) increases AT lipolysis by activation of classic and inflammatory lipolytic pathways and reduction of insulin sensitivity. In experiment 1, subcutaneous AT (SCAT) explants were collected from periparturient (n = 12) Holstein cows at 11 ± 3.6 d (mean ± SE) before calving, and 6 ± 1 d and 13 ± 1.4 d after parturition. Explants were treated with the endotoxin lipopolysaccharide (LPS; 20 µg/mL; basal = 0 µg/mL) for 3 h. The effect of LPS on lipolysis was assessed in the presence of the β-adrenergic agonist and promoter of lipolysis isoproterenol (ISO; 1 µM; LPS+ISO). In experiment 2, SCAT explants were harvested from 24 nonlactating, nongestating multiparous Holstein dairy cows and exposed to the same treatments as in experiment 1 for 3 and 7 h. The effect of LPS on the antilipolytic responses induced by insulin (INS = 1 µL/L, LPS+INS) was established during ISO stimulation [ISO+INS, LPS+ISO+INS]. The characterization of lipolysis included the quantification of glycerol release and the assessment of markers of lipase activity [adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and phosphorylated HSL Ser563 (pHSL)], and insulin pathway activation (AKT, pAKT) using capillary electrophoresis. Inflammatory gene networks were evaluated by real-time quantitative PCR. In periparturient cows, LPS increased AT lipolysis by 67 ± 12% at 3 h across all time points compared with basal. In nonlactating cows, LPS was an effective lipolytic agent at 3 h and 7 h, increasing glycerol release by 115 ± 18% and 68.7 ± 16%, respectively, relative to basal. In experiment 2, LPS enhanced ATGL activity with minimal HSL activation at 3 h. In contrast, at 7 h, LPS increased HSL phosphorylation (i.e., HSL activity) by 123 ± 11%. The LPS-induced HSL lipolytic activity at 7 h coincided with the activation of the MEK/ERK inflammatory pathway. In experiment 2, INS reduced the lipolytic effect of ISO (ISO+INS: -63 ± 18%) and LPS (LPS+INS: -45.2 ± 18%) at 3 h. However, the antilipolytic effect of INS was lost in the presence of LPS at 7 h (LPS+INS: -16.3 ± 16%) and LPS+ISO+INS at 3 and 7 h (-3.84 ± 23.6% and -21.2 ± 14.6%). Accordingly, LPS reduced pAKT:AKT (0.11 ± 0.07) compared with basal (0.18 ± 0.05) at 7 h. Our results indicated that exposure to LPS activated the classic and inflammatory lipolytic pathways and reduced insulin sensitivity in SCAT. These data provide evidence that during endotoxemia, dairy cows may be more susceptible to lipolysis dysregulation and loss of adipocyte sensitivity to the antilipolytic action of insulin.
Topics: Adipose Tissue; Animals; Cattle; Cattle Diseases; Female; Insulin Resistance; Lipolysis; Lipopolysaccharides; Sterol Esterase
PubMed: 34696909
DOI: 10.3168/jds.2021-20855 -
Frontiers in Endocrinology 2021Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the... (Review)
Review
Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the epidemic of metabolic syndromes such as obesity and type 2 diabetes. These thermogenic fats implement mitochondrial oxidative phosphorylation and uncouple respiration to catabolize fatty acids and glucose, which leads to an increase in energy expenditure. In particular, beige adipocytes that arise in white adipose tissue display their thermogenic capacity through various noncanonical mechanisms. This review aims to summarize the general overview of thermogenic fat, especially including the UCP1-independent adaptive thermogenesis and the emerging mechanisms of "beiging", which may provide more evidence of targeting thermogenic fat to counteract obesity and other metabolic disorders in humans.
Topics: Adipocytes, Beige; Adipose Tissue; Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Energy Metabolism; Humans; Lipid Metabolism; Lipolysis; Thermogenesis
PubMed: 34367068
DOI: 10.3389/fendo.2021.696505 -
Trends in Pharmacological Sciences Apr 2016The increasing epidemic of obesity and its comorbidities has spurred research interest in adipose biology and its regulatory functions. Recent studies have revealed that... (Review)
Review
The increasing epidemic of obesity and its comorbidities has spurred research interest in adipose biology and its regulatory functions. Recent studies have revealed that the mechanistic target of rapamycin (mTOR) signaling pathway has a critical role in the regulation of adipose tissue function, including adipogenesis, lipid metabolism, thermogenesis, and adipokine synthesis and/or secretion. Given the importance of mTOR signaling in controlling energy homeostasis, it is not unexpected that deregulated mTOR signaling is associated with obesity and related metabolic disorders. In this review, we highlight current advances in understanding the roles of the mTOR signaling pathway in adipose tissue. We also provide a more nuanced view of how the mTOR signaling pathway regulates adipose tissue biology and function. Finally, we describe approaches to modulate the activity and tissue-specific function of mTOR that may pave the way towards counteracting obesity and related metabolic diseases.
Topics: Adipose Tissue; Animals; Humans; Lipogenesis; Lipolysis; Molecular Targeted Therapy; Obesity; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 26700098
DOI: 10.1016/j.tips.2015.11.011 -
Current Opinion in Cell Biology Jun 2023Lipid droplets (LDs) are major lipid storage organelles, sequestering energy-rich triglycerides and serving as nutrient sinks for cellular homeostasis. Observed for over... (Review)
Review
Lipid droplets (LDs) are major lipid storage organelles, sequestering energy-rich triglycerides and serving as nutrient sinks for cellular homeostasis. Observed for over a century but generally ignored, LDs are now appreciated to play key roles in organismal physiology and disease. They also form numerous functional contacts with other organelles. Here, we highlight recent studies examining LDs from distinct perspectives of their life cycle: their biogenesis, "social" life as they interact with other organelles, and deaths via lipolysis or lipophagy. We also discuss recent work showing how changes in LD lipid content alter the biophysical phases of LD lipids, and how this may fine-tune the LD protein landscape and ultimately LD function.
Topics: Lipid Droplets; Lipolysis; Lipid Metabolism; Triglycerides; Proteins
PubMed: 37295067
DOI: 10.1016/j.ceb.2023.102178 -
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