FRI-348-Monoacylglycerol lipase deletion protects against obesity-induced hepatic steatosis via PPARg regulation in adipose tissue and fatty acid malabsorption in the intestine

Abstract Objectives We tested whether the scavenger receptor, class B type 1 (SR-B1), a physiologically relevant HDL receptor, modulates the metabolic and inflammatory phenotype of obese mice, accompanied by changes in adipocyte and hepatocyte lipid deposits. Methods Male SR-B1 knock-out (KO) mice and wild-type (WT) littermates were fed for 12 weeks with a high-fat diet (HFD, n = 12 per group) to induce obesity. Animals were euthanized after overnight food deprivation. Blood was obtained and adipose tissue and liver were removed. Plasma or frozen tissues were used for biochemical analyses or assessed by light microscopy and immunohistochemistry. Comparisons between WT and KO mice fed with HFD were performed and differences were considered statistically significant when P < 0.05. Results Compared to obese WT, obese HFD-fed SR-B1 KO mice showed increased plasma total cholesterol (p < 0.0001) and triglycerides (TG) (p < 0.01) as well as tumor necrosis factor-α (TNF-α) (p < 0.0001) levels. Also, these animals exhibited white fat with larger adipocytes (p < 0.0001) and increased macrophage-based crown-like structure formation (p < 0.01), compared to HFD-fed WT mice, revealing a more inflammatory adipose tissue. These changes in adipose tissue were associated with reduced hepatic steatosis: reduced hepatocyte lipid droplet area (p < 0.0001) and decreased liver TG content (p < 0.0001). In addition, obese SR-B1-deficient mice showed reduced hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) expression, more efficient hepatic fatty acid β-oxidation and increased very-low-density lipoprotein (VLDL)-TG secretion compared to obese HFD-fed WT mice Furthermore, liver fatty acid (FA) composition in obese SR-B1-deficient mice revealed a reduction in monounsaturated (MUFA) (p < 0.01), but an increase in polyunsaturated (PUFA) (p < 0.05), fatty acid content, compared to obese WT mice. Conclusions Our findings demonstrate that SR-B1 expression modulates high fat feeding-associated inflammatory dyslipidemia, adipocyte hypertrophy, and hepatic steatosis; key processes underlying the pathogenesis of highly prevalent chronic diseases, such as obesity and non-alcoholic fatty liver disease (NAFLD). Funding Sources FONDECYT 1,150,399, FONDECYT 1,180,525.

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Human hepatic lipase overexpression in mice induces hepatic steatosis and obesity through promoting hepatic lipogenesis and white adipose tissue lipolysis and fatty acid uptake

PLoS ONE ◽

10.1371/journal.pone.0189834 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0189834 ◽

Cited By ~ 5

Author(s):

Lídia Cedó ◽

David Santos ◽

Núria Roglans ◽

Josep Julve ◽

Victor Pallarès ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Hepatic Steatosis ◽

White Adipose Tissue ◽

Hepatic Lipase ◽

Fatty Acid Uptake ◽

Acid Uptake ◽

Hepatic Lipogenesis ◽

Adipose Tissue Lipolysis

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Combined Ethanol Extract of Grape Pomace and Omija Fruit Ameliorates Adipogenesis, Hepatic Steatosis, and Inflammation in Diet-Induced Obese Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/212139 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Su-Jung Cho ◽

Un Ju Jung ◽

Hae-Jin Park ◽

Hye-Jin Kim ◽

Yong Bok Park ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Fatty Liver ◽

Hepatic Steatosis ◽

White Adipose Tissue ◽

Ethanol Extract ◽

Grape Pomace ◽

Control Group ◽

Acid Oxidation ◽

Obese Mice

The aim of this study was to evaluate the long-term effects of grape pomace ethanol extract (GPE) with or without omija fruit ethanol extract (OFE) on adiposity, hepatic steatosis, and inflammation in diet-induced obese mice. Male C57BL/6J mice were fed a high-fat diet (HFD) as the control diet and HFD plus GPE (0.5%, w/w) with or without OFE (0.05%, w/w) as the experimental diet for 12 weeks. GPE alone did not significantly affect adipogenesis and hepatic steatosis. However, the supplementation of GPE + OFE significantly lowered body weight gain, white adipose tissue weight, adipocyte size, and plasma free fatty acid and adipokines (leptin, PAI-1, IL-6, and MCP-1) levels in HFD-fed mice compared to those of the control group. These beneficial effects of GPE + OFE were partly related to the decreased expression of lipogenic and inflammatory genes in white adipose tissue. GPE + OFE supplementation also significantly lowered liver weight and ameliorated fatty liver by inhibiting expression of hepatic genes involved in fatty acid and cholesterol syntheses as well as inflammation and by activating hepatic fatty acid oxidation. These findings suggest that the combined ethanol extract of grape pomace and omija fruit has the potential to improve adiposity and fatty liver in diet-induced obese mice.

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Ovariectomy-Induced Hepatic Lipid and Cytochrome P450 Dysmetabolism Precedes Serum Dyslipidemia

International Journal of Molecular Sciences ◽

10.3390/ijms22094527 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4527

Author(s):

Hana Malinská ◽

Martina Hüttl ◽

Denisa Miklánková ◽

Jaroslava Trnovská ◽

Iveta Zapletalová ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Brown Adipose Tissue ◽

Hepatic Steatosis ◽

Fatty Acid Oxidation ◽

Acid Oxidation ◽

Hepatic Triglyceride ◽

Tissue Weight ◽

Triglyceride Accumulation ◽

Brown Adipose

Ovarian hormone deficiency leads to increased body weight, visceral adiposity, fatty liver and disorders associated with menopausal metabolic syndrome. To better understand the underlying mechanisms of these disorders in their early phases of development, we investigated the effect of ovariectomy on lipid and glucose metabolism. Compared to sham-operated controls, ovariectomized Wistar female rats markedly increased whole body and visceral adipose tissue weight (p ˂ 0.05) and exhibited insulin resistance in peripheral tissues. Severe hepatic triglyceride accumulation (p ˂ 0.001) after ovariectomy preceded changes in both serum lipids and glucose intolerance, reflecting alterations in some CYP proteins. Increased CYP2E1 (p ˂ 0.05) and decreased CYP4A (p ˂ 0.001) after ovariectomy reduced fatty acid oxidation and induced hepatic steatosis. Decreased triglyceride metabolism and secretion from the liver contributed to hepatic triglyceride accumulation in response to ovariectomy. In addition, interscapular brown adipose tissue of ovariectomized rats exhibited decreased fatty acid oxidation (p ˂ 0.01), lipogenesis (p ˂ 0.05) and lipolysis (p ˂ 0.05) despite an increase in tissue weight. The results provide evidence that impaired hepatic triglycerides and dysregulation of some CYP450 proteins may have been involved in the development of hepatic steatosis. The low metabolic activity of brown adipose tissue may have contributed to visceral adiposity as well as triglyceride accumulation during the postmenopausal period.

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Thermoneutrality Inhibits Thermogenic Markers and Exacerbates Nonalcoholic Fatty Liver in Mice (P21-068-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz041.p21-068-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Lei Hao ◽

Md Shahjalal Hossain Khan ◽

Yujiao Zu ◽

Jie Liu ◽

Shu Wang

Keyword(s):

Drinking Water ◽

Body Weight ◽

Adipose Tissue ◽

Fatty Acid ◽

Liver Disease ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Chow Diet ◽

Nonalcoholic Fatty Liver ◽

Brown Adipose

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting more than a third of the US population and 25% of the global population. In this study, we investigated whether manipulation of brown adipose tissue (BAT) activity via housing C57BL/6 J mice under two different housing temperatures (22°C vs 27°C) influences the development of NAFLD. Methods Male C57BL/6 J mice were randomly allocated to 4 groups (8 mice/group). Briefly, mice housed at the standard temperature (ST) (22°C) or thermoneutral temperature (TT) (27°C) were fed either a control chow diet (CHD) (Picolab rodent diet 20, LabDiet) with a regular drinking water or an “fast food” diet (FFD) (Research Diets, D12079B) plus fructose 23.1 g/L and glucose 18.9 g/L added to the drinking water for 10 weeks. Results Mice under TT had significant less food intake compared to their counter partners under ST, regardless of diets. Mice exposed to TT and fed FFD had the highest body weight and plasma leptin level among all groups. For mice fed CHD, mice at TT did not present hepatic steatosis although they slightly gained more body weight compared to mice at ST. For mice fed FFD, thermoneutral housing mice had greater liver weight, liver triglyceride, and exacerbated hepatic steatosis compared to the standard housing mice. Moreover, for mice fed FFD, TT compared to ST had significantly elevated expression of fatty acid synthase, sterol regulatory element-binding transcription factor 1, fatty acid translocase, and monocyte chemoattractant protein-1 in liver. By contrast, TT did not change expression of above genes in mice fed CHD. Furthermore, thermoneutrally housed mice displayed a decrease in gene expression of thermogenic markers, such as uncoupling protein 1, elongation of very long chain fatty acids 3, and cell death-inducing DNA fragmentation factor alpha-like effector A in BAT and inguinal white adipose tissue (WAT). Conclusions Thermoneutrality inhibits expression of thermogenic markers in both BAT and WAT, which correlated to exacerbated NAFLD in mice. Our data indicate that activating BAT and/or promoting WAT browning may represent a potential strategy for the management of NAFLD. Funding Sources The College of Human Sciences of Texas Tech University; the National Center for Complementary & Integrative Health.

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Lack of monoacylglycerol lipase prevents hepatic steatosis by favoring lipid storage in adipose tissue and intestinal malabsorption

The Journal of Lipid Research ◽

10.1194/jlr.m093369 ◽

2019 ◽

Vol 60 (7) ◽

pp. 1284-1292 ◽

Cited By ~ 6

Author(s):

Matteo Tardelli ◽

Francesca V. Bruschi ◽

Thierry Claudel ◽

Claudia D. Fuchs ◽

Nicole Auer ◽

...

Keyword(s):

Adipose Tissue ◽

Hepatic Steatosis ◽

Lipid Storage ◽

Monoacylglycerol Lipase ◽

Intestinal Malabsorption

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A mouse model of Long-Chain 3-Ketoacyl-CoA Thiolase deficlency of mitochondrial fatty acid beta-oxidation is associated with low body mass, cold intoterance and hepatic steatosis

Gastroenterology ◽

10.1016/s0016-5085(01)80526-6 ◽

2001 ◽

Vol 120 (5) ◽

pp. A107-A107

Author(s):

R MERRIMAN ◽

W QIN ◽

A STRAUSS

Keyword(s):

Fatty Acid ◽

Mouse Model ◽

Hepatic Steatosis ◽

Body Mass ◽

Beta Oxidation ◽

Mitochondrial Fatty Acid ◽

Fatty Acid Beta Oxidation ◽

Long Chain

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Platelet Aggregation in Finnish Men and Its Relation to Fatty Acids in Platelets, Plasma and Adipose Tissue

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660071 ◽

1985 ◽

Vol 54 (03) ◽

pp. 563-569 ◽

Cited By ~ 19

Author(s):

M K Salo ◽

E Vartiainen ◽

P Puska ◽

T Nikkari

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Platelet Aggregation ◽

Acid Composition ◽

Saturated Fatty Acids ◽

Free Living ◽

Ω3 Fatty Acids ◽

Induced Aggregation

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.

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