High-Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for In Vitro Studies

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

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An ethanolic extract of Artemisia scoparia inhibits lipolysis in vivo and has antilipolytic effects on murine adipocytes in vitro

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00177.2018 ◽

2018 ◽

Vol 315 (5) ◽

pp. E1053-E1061 ◽

Cited By ~ 4

Author(s):

Anik Boudreau ◽

Allison J. Richard ◽

Jasmine A. Burrell ◽

William T. King ◽

Ruth Dunn ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Free Fatty Acid ◽

Microarray Analysis ◽

High Fat Diet ◽

Ethanolic Extract ◽

High Fat ◽

Artemisia Scoparia

An ethanolic extract of Artemisia scoparia (SCO) has metabolically favorable effects on adipocyte development and function in vitro and in vivo. In diet-induced obese mice, SCO supplementation significantly reduced fasting glucose and insulin levels. Given the importance of adipocyte lipolysis in metabolic health, we hypothesized that SCO modulates lipolysis in vitro and in vivo. Free fatty acids and glycerol were measured in the sera of mice fed a high-fat diet with or without SCO supplementation. In cultured 3T3-L1 adipocytes, the effects of SCO on lipolysis were assessed by measuring glycerol and free fatty acid release. Microarray analysis, qPCR, and immunoblotting were used to assess gene expression and protein abundance. We found that SCO supplementation of a high-fat diet in mice substantially reduces circulating glycerol and free fatty acid levels, and we observed a cell-autonomous effect of SCO to significantly attenuate tumor necrosis factor-α (TNFα)-induced lipolysis in cultured adipocytes. Although several prolipolytic and antilipolytic genes were identified by microarray analysis of subcutaneous and visceral adipose tissue from SCO-fed mice, regulation of these genes did not consistently correlate with SCO’s ability to reduce lipolytic metabolites in sera or cell culture media. However, in the presence of TNFα in cultured adipocytes, SCO induced antilipolytic changes in phosphorylation of hormone-sensitive lipase and perilipin. Together, these data suggest that the antilipolytic effects of SCO on adipose tissue play a role in the ability of this botanical extract to improve whole body metabolic parameters and support its use as a dietary supplement to promote metabolic resiliency.

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High Fat Diet Administration during Specific Periods of Pregnancy Alters Maternal Fatty Acid Profiles in the Near-Term Rat

Nutrients ◽

10.3390/nu8010025 ◽

2016 ◽

Vol 8 (1) ◽

pp. 25 ◽

Cited By ~ 10

Author(s):

Marlon Cerf ◽

Emilio Herrera

Keyword(s):

Fatty Acid ◽

High Fat Diet ◽

Fatty Acid Profiles ◽

High Fat ◽

Near Term

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Circulating pro fibrotic protein promotes fibrosis in liver

European Heart Journal ◽

10.1093/ehjci/ehaa946.3740 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

Y Hsiao ◽

I Shimizu ◽

Y Yoshida ◽

R Ikegami ◽

Y Hayashi ◽

...

Keyword(s):

Liver Fibrosis ◽

High Fat Diet ◽

In Vitro Studies ◽

High Fat ◽

Brown Adipocytes ◽

Adipose Tissues ◽

Nash Model ◽

Brown Adipose

Abstract Background/Introduction Non-alcoholic steatohepatitis (NASH), driven by the obesity epidemic, has become the most common form of liver disease. Inflamed visceral adipose tissue secretes pro-inflammatory adipokines that are causal for systemic metabolic disorders. Role of adipokines in NASH, especially those from brown adipose tissues (BATokine) remain unclear. Purpose To show the pathogenic role of BATokine in NASH. Methods To identify and characterize the pathological roles of pro-fibrotic BATokine, we generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice, and murine systemic or BAT specific knockout (KO) models. We also conducted functional in-vitro studies with differentiated brown adipocytes. Results Analyzing two sets of DNA micro array data with bioinformatics, we identified a secreted form pro-fibrotic protein (sPFP) expressed in dysfunctional brown adipose tissues (BAT) in mice. Testing our biobank samples, we found this protein increased in plasma of NASH patients. We generated a murine obese NASH model by imposing a high fat diet in C57BL6/NCr mice for 9–10 months since 4 weeks of age, and found that sPFP is produced predominantly by BAT. In this model, we also found that sPFP increased in plasma. We generated a murine systemic or BAT specific sPFP knockout (KO) models and found that liver fibrosis ameliorated in these models. We also suppressed circulating sPFP with a peptide vaccine targeting this molecule, and found that sPFP vaccination therapy inhibited liver fibrosis. Next, we generated sPFP gain of function (GOF) model by the administration of plasmid encoding sPFP into skeletal muscle. Liver fibrosis augmented in sPFP-GOF model, and these results suggested that sPFP has causal role for the progression of fibrotic response in liver. In vitro studies with differentiated brown adipocytes showed that metabolic stress increased c-Fos in nuclear, and this was causal for an increase in sPFP level. Conclusions Our results suggest that one of the BATokines, sPFP, contributes for the progression of fibrotic responses in obese-NASH model. Inhibition of sPFP may become a therapy for NASH or obesity related fibrotic disorders. Funding Acknowledgement Type of funding source: None

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Lactobacillus rhamnosus GG and Oat Beta‐Glucan Regulated Fatty Acid Profiles along the Gut‐Liver‐Brain Axis of Mice Fed with High Fat Diet and Demonstrated Antioxidant and Anti‐Inflammatory Potentials

Molecular Nutrition & Food Research ◽

10.1002/mnfr.202000566 ◽

2020 ◽

Vol 64 (18) ◽

pp. 2000566 ◽

Cited By ~ 1

Author(s):

Yu Fung Yau ◽

Hani El‐Nezami ◽

Jean‐Marie Galano ◽

Zuzanna Maria Kundi ◽

Thierry Durand ◽

...

Keyword(s):

Fatty Acid ◽

High Fat Diet ◽

Lactobacillus Rhamnosus ◽

Fatty Acid Profiles ◽

High Fat ◽

Beta Glucan ◽

Lactobacillus Rhamnosus Gg ◽

Anti Inflammatory

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Loss of macrophage fatty acid oxidation does not potentiate systemic metabolic dysfunction

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00408.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. E381-E393 ◽

Cited By ~ 19

Author(s):

Elsie Gonzalez-Hurtado ◽

Jieun Lee ◽

Joseph Choi ◽

Ebru S. Selen Alpergin ◽

Samuel L. Collins ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Oxidation ◽

High Fat Diet ◽

Macrophage Polarization ◽

Acid Oxidation ◽

Causative Role ◽

Metabolic Dysfunction ◽

High Fat ◽

Diet Induced Obesity

Fatty acid oxidation in macrophages has been suggested to play a causative role in high-fat diet-induced metabolic dysfunction, particularly in the etiology of adipose-driven insulin resistance. To understand the contribution of macrophage fatty acid oxidation directly to metabolic dysfunction in high-fat diet-induced obesity, we generated mice with a myeloid-specific knockout of carnitine palmitoyltransferase II (CPT2 Mϕ-KO), an obligate step in mitochondrial long-chain fatty acid oxidation. While fatty acid oxidation was clearly induced upon IL-4 stimulation, fatty acid oxidation-deficient CPT2 Mϕ-KO bone marrow-derived macrophages displayed canonical markers of M2 polarization following IL-4 stimulation in vitro. In addition, loss of macrophage fatty acid oxidation in vivo did not alter the progression of high-fat diet-induced obesity, inflammation, macrophage polarization, oxidative stress, or glucose intolerance. These data suggest that although IL-4-stimulated alternatively activated macrophages upregulate fatty acid oxidation, fatty acid oxidation is dispensable for macrophage polarization and high-fat diet-induced metabolic dysfunction. Macrophage fatty acid oxidation likely plays a correlative, rather than causative, role in systemic metabolic dysfunction.

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Nonacute effects of H-FABP deficiency on skeletal muscle glucose uptake in vitro

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00139.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. E977-E982 ◽

Cited By ~ 14

Author(s):

Erdal Erol ◽

Gary W. Cline ◽

Jason K. Kim ◽

Heinrich Taegtmeyer ◽

Bert Binas

Keyword(s):

Skeletal Muscle ◽

Fatty Acid ◽

Glucose Uptake ◽

Soleus Muscle ◽

High Fat Diet ◽

High Fat ◽

Insulin Dependent ◽

Muscle Triglyceride ◽

Long Chain

Heart-type fatty acid-binding protein (H-FABP) is required for high rates of skeletal muscle long-chain fatty acid (LCFA) oxidation and esterification. Here we assessed whether H-FABP affects soleus muscle glucose uptake when measured in vitro in the absence of LCFA. Wild-type and H-FABP null mice were fed a standard chow or high-fat diet before muscle isolation. With the chow, the mutation increased insulin-dependent deoxyglucose uptake by 141% ( P < 0.01) at 0.02 mU/ml of insulin but did not cause a significant effect at 2 mU/ml of insulin; skeletal muscle triglyceride and long-chain acyl-CoA (LCA-CoA) levels remained normal. With the high-fat diet, the mutation increased insulin-dependent deoxyglucose uptake by 190% ( P < 0.01) at 2 mU/ml of insulin, thus partially preventing insulin resistance, and it completely prevented the threefold ( P < 0.001) diet-induced increase of muscle triglyceride levels; however, muscle LCA-CoA levels showed little or no reduction. With both diets, the mutation reduced the basal (insulin-independent) soleus muscle deoxyglucose uptake by 28% ( P < 0.05). These results establish a close relation between FABP-dependent lipid pools and insulin sensitivity and indicate the existence of a nonacute, antagonistic, and H-FABP-dependent fatty acid regulation of basal and insulin-dependent muscle glucose uptake.

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