Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice

Abstract Large yellow croaker roe phospholipids (LYCRPLs) has great nutritional value because of containing rich docosahexaenoic acid (DHA), which is a kind of n-3 polyunsaturated fatty acids (n-3 PUFAs). In...

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Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000783 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000783 ◽

Cited By ~ 7

Author(s):

Liang Xu ◽

Naoto Nagata ◽

Guanliang Chen ◽

Mayumi Nagashimada ◽

Fen Zhuge ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Energy Expenditure ◽

Chronic Inflammation ◽

Plasma Levels ◽

High Fat Diet ◽

Macrophage Activation ◽

Low Grade ◽

Obese Mice ◽

High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

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EPA/DHA Concentrate by Urea Complexation Decreases Hyperinsulinemia and Increases Plin5 in the Liver of Mice Fed a High-Fat Diet

Molecules ◽

10.3390/molecules25143289 ◽

2020 ◽

Vol 25 (14) ◽

pp. 3289

Author(s):

Alejandra Espinosa ◽

Andrés Ross ◽

Gretel Dovale-Rosabal ◽

Francisco Pino-de la Fuente ◽

Ernesto Uribe-Oporto ◽

...

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

High Fat Diet ◽

Fasting Insulin ◽

Obese Mice ◽

High Fat ◽

Insulin Resistant ◽

Associated Proteins ◽

Total Fatty Acids ◽

Fish Oil Supplementation

Dietary intake of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) reduces insulin resistance and hepatic manifestations through the regulation of metabolism in the liver. Obese mice present insulin resistance and lipid accumulation in intracellular lipid droplets (LDs). LD-associated proteins perilipin (Plin) have an essential role in both adipogenesis and lipolysis; Plin5 regulates lipolysis and thus contributes to fat oxidation. The purpose of this study was to compare the effects of deodorized refined salmon oil (DSO) and its polyunsaturated fatty acids concentrate (CPUFA) containing EPA and DHA, obtained by complexing with urea, on obesity-induced metabolic alteration. CPUFA maximum content was determined using the Box–Behnken experimental design based on Surface Response Methodology. The optimized CPUFA was administered to high-fat diet (HFD)-fed mice (200 mg/kg/day of EPA + DHA) for 8 weeks. No significant differences (p > 0.05) in cholesterol, glycemia, LDs or transaminase content were found. Fasting insulin and hepatic Plin5 protein level increased in the group supplemented with the EPA + DHA optimized product (38.35 g/100 g total fatty acids) compared to obese mice without fish oil supplementation. The results suggest that processing salmon oil by urea concentration can generate an EPA+DHA dose useful to prevent the increase of fasting insulin and the decrease of Plin5 in the liver of insulin-resistant mice.

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Increased Capacity of Distal Intestinal Epithelium to Transport Long-Chain Fatty Acids in Obese Mice Fed a High-Fat Diet

10.1210/endo-meetings.2011.part1.or5.or04-4 ◽

2011 ◽

pp. OR04-4-OR04-4

Author(s):

Matthew D Lynes ◽

Rachel Fogley ◽

Eric P Widmaier

Keyword(s):

Fatty Acids ◽

Intestinal Epithelium ◽

High Fat Diet ◽

Long Chain Fatty Acids ◽

Obese Mice ◽

High Fat ◽

Long Chain ◽

Chain Fatty Acids

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Capsosiphon fulvescensextracts improve obesity-associated metabolic disorders and hepatic steatosis in high-fat diet-induced obese mice

Animal Science Journal ◽

10.1111/asj.12969 ◽

2017 ◽

Vol 89 (3) ◽

pp. 589-596 ◽

Cited By ~ 1

Author(s):

Mi-Young Yun ◽

Jae-Sug Lee ◽

Byoung-Soo Kim ◽

Hwa-Jung Choi

Keyword(s):

Hepatic Steatosis ◽

High Fat Diet ◽

Metabolic Disorders ◽

Obese Mice ◽

High Fat

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Decreasing the Dietary Ratio of Linoleic Acid (n-6) and Alpha-linolenic Acid (n-3) Does Not Reduce Adiposity or Mitigate Bone Deterioration of Obese Mice (P08-096-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.p08-096-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Jay Cao ◽

Kim Michelsen ◽

Brian Gregoire ◽

Matthew Picklo

Keyword(s):

Fatty Acids ◽

Linoleic Acid ◽

Bone Resorption ◽

Linolenic Acid ◽

High Fat Diet ◽

Bone Structure ◽

Bone Resorption Marker ◽

Obese Mice ◽

High Fat ◽

Alpha Linolenic Acid

Abstract Objectives To investigate whether the ratio of n-6: n-3 mainly as linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3), when ALA was kept constant, affects adiposity or adiposity-induced changes in bone structure in mice fed a high-fat diet. Since LA is a precursor for arachidonic acid which is the substrate for certain proinflammatory eicosanoids, n-6 fatty acids have been considered to promote inflammation, whereas n-3 fatty acids are considered to have anti-inflammatory properties. Studies show adiposity and inflammation are inversely associated bone mass. Therefore, we hypothesized that decreasing dietary LA content (n-6: n-3 ratio) mitigates high-fat diet (HF) induced adiposity and bone loss. Methods Fifty-two male C57BL/6 mice at 6-wk-old were randomly assigned to 4 treatment groups (n = 13/group) and fed one of the diets as described in the Table below ad libitum for 6 months: a normal-fat diet (NF, 10%en) with n-6 at 6%en or HF diets (45%en) with n-6 at either 9%, 6%, or 3%en, respectively. ALA content in the diets was kept the same for all groups at 1%en, which is above the minimum requirement (0.68%en) for rodents. Diets were formulated with a combination of high oleic sunflower oil, palm oil, safflower oil and flaxseed oil to achieve desired levels of fatty acids. Results Compared to the NF, the HF increased fat mass, percentage body fat, trabecular separation, serum bone resorption marker (tartrate-resistant acid phosphatase), and decreased bone volume/total volume (P < 0.05). The ratio of n-6: n-3 did not significantly affect fat mass, serum bone resorption marker, or any bone structural parameters. Conclusions These data indicate that decreasing the dietary n-6: n-3 ratio by reducing LA intake does not reduce adiposity or improve bone structure in obese mice. Funding Sources USDA ARS Project no. 3062-51000-053-00D. Supporting Tables, Images and/or Graphs

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6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2021.112491 ◽

2022 ◽

Vol 146 ◽

pp. 112491

Author(s):

Zhe Cheng ◽

Xinyu Xiong ◽

Yi Zhou ◽

Fan Wu ◽

Qingqing Shao ◽

...

Keyword(s):

High Fat Diet ◽

Metabolic Disorders ◽

Obese Mice ◽

High Fat

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Maternal N-Acetyl Cysteine Intake Improved Glucose Tolerance in Obese Mice Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms21061981 ◽

2020 ◽

Vol 21 (6) ◽

pp. 1981

Author(s):

Michal Michlin ◽

Lital Argaev-Frenkel ◽

Liza Weinstein-Fudim ◽

Asher Ornoy ◽

Tovit Rosenzweig

Keyword(s):

Environmental Factors ◽

Glucose Tolerance ◽

High Fat Diet ◽

Early Life ◽

Metabolic Disorders ◽

Obese Mice ◽

High Fat ◽

Pregnancy And Lactation ◽

Glucose Stimulated Insulin Secretion

Exposure to certain environmental factors during the early stages of development was found to affect health in adulthood. Among other environmental factors, oxidative stress has been suggested to be involved in fetal programming, leading to elevated risk for metabolic disorders, including type 2 diabetes; however, the possibility that antioxidant consumption during early life may affect the development of diabetes has scarcely been studied. The aim of this study was to investigate the effects of N-acetyl-l-cysteine (NAC) given during pregnancy and lactation on the susceptibility of offspring to develop glucose intolerance at adulthood. C57bl6/J mice were given NAC during pregnancy and lactation. High fat diet (HFD) was given to offspring at an age of 6 weeks for an additional 9 weeks, till the end of the study. Isolated islets of NAC-treated offspring (6 weeks old, before HFD feeding) had an increased efficacy of glucose-stimulated insulin secretion and a higher resistance to oxidative damage. Following HFD feeding, glucose tolerance and insulin sensitivity of NAC-treated offspring were improved. In addition, islet diameter was lower in male offspring of NAC-treated mice compared to their HFD-fed littermates. NAC consumption during early life improves glucose tolerance in adulthood in mice.

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Dietary Annatto-Extracted Tocotrienol Reduces Inflammation and Oxidative Stress, and Improves Macronutrient Metabolism in Obese Mice: A Metabolic Profiling Study

Nutrients ◽

10.3390/nu13041267 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1267

Author(s):

Chwan-Li Shen ◽

Sivapriya Ramamoorthy ◽

Gurvinder Kaur ◽

Jannette M. Dufour ◽

Rui Wang ◽

...

Keyword(s):

Oxidative Stress ◽

High Fat Diet ◽

Metabolic Disorders ◽

Essential Amino Acids ◽

Obese Mice ◽

High Fat ◽

Toxic Dose ◽

Serum Metabolites ◽

Stress Markers ◽

And Oxidative Stress

Obesity and its related complications are a world-wide health problem. Dietary tocotrienols (TT) have been shown to improve obesity-associated metabolic disorders, such as hypercholesterolemia, hyperglycemia, and gut dysbiosis. This study examined the hypothesis that the antioxidant capacity of TT alters metabolites of oxidative stress and improves systemic metabolism. C57BL/6J mice were fed either a high-fat diet (HFD control) or HFD supplemented with 800 mg annatto-extracted TT/kg (HFD+TT800) for 14 weeks. Sera from obese mice were examined by non-targeted metabolite analysis using UHPLC/MS. Compared to the HFD group, the HFD+TT800 group had higher levels of serum metabolites, essential amino acids (lysine and methionine), sphingomyelins, phosphatidylcholine, lysophospholipids, and vitamins (pantothenate, pyridoxamine, pyridoxal, and retinol). TT-treated mice had lowered levels of serum metabolites, dicarboxylic fatty acids, and inflammatory/oxidative stress markers (trimethylamine N-oxide, kynurenate, 12,13-DiHOME, and 13-HODE + 9-HODE) compared to the control. The results suggest that TT supplementation lowered inflammation and oxidative stress (oxidized glutathione and GSH/GSSH) and improved macronutrient metabolism (carbohydrates) in obese mice. Thus, TT actions on metabolites were beneficial in reducing obesity-associated hypercholesterolemia/hyperglycemia. The effects of a non-toxic dose of TT in mice support the potential for clinical applications in obesity and metabolic disease.

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