scholarly journals GW29-e0692 Branched Chain Amino Acids Attenuates Hepatic Akt Signaling and Results in Severe Liver Metabolic Disorder in High Fat Diets Induced Obese Mice

2018 ◽  
Vol 72 (16) ◽  
pp. C83-C84
Author(s):  
Huishou Zhao ◽  
Feng Yan ◽  
Shan Wang ◽  
Xiaomeng Zhang ◽  
Huaning Xie ◽  
...  
Keyword(s):  
Amino Acids ◽  
Metabolic Disorder ◽  
Branched Chain Amino Acids ◽  
Akt Signaling ◽  
Obese Mice ◽  
High Fat ◽  
Severe Liver ◽  
High Fat Diets ◽  
Branched Chain ◽  
Fat Diets

scholarly journals Dietary phosphatidylcholine promotes breast cancer in the hyperlipidemic E0771 murine model

2020 ◽  
Author(s):  
Fredrick O Onono ◽  
Lakshman Chelvarajan ◽  
Baoxiang Yan ◽  
Ebubechi Adindu ◽  
Esias Bedingar
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Amino Acids ◽  
Tumor Growth ◽  
Cancer Development ◽  
Primary Breast Tumor ◽  
High Fat ◽  
Breast Cancer Development ◽  
High Fat Diets ◽  
Fat Diets

Abstract BackgroundCancer cells are characterized by aberrant phosphatidylcholine (PC) metabolism. PC can be synthesized de novo or absorbed from diet, after digestion, by the intestinal enterocytes. Here, we investigated the association of dietary intake of PC and breast cancer development in mice. MethodsWe used tandem mass spectrometry methods to quantitate PC content of various fat sources used to manufacture rodent diets. Rodent diets were then formulated with either casein or amino acids in place of casein. To test the effects of dietary PC on tumor growth we fed low density lipoprotein receptor-null (LDLR–/–) mice high fat diets formulated with casein (high PC) or amino acids in place of casein (low PC). Endogenous PC biosynthesis and levels of total circulated plasma PC was monitored using stable isotope tracer choline and mass spectrometry analysis. Tumors were induced in mice after 12 weeks of high fat diet feeding. Since PC-derived molecules are important transducers of mitogenic signals, we tested the effects of inhibiting production of lysophosphatidic acid (LPA) using a recently described autotaxin (ATX) inhibitor. Finally, plasma inflammatory cytokine levels were analyzed to determine the effects of diets and ATX inhibition on systemic cytokine milieu. ResultsWe found that casein is the main source of PC when present in rodent diets. Replacing casein with amino acids increased the relative proportion of endogenously biosynthesized PC in mouse plasma. Compared to diets containing casein, amino acid-defined diets decreased primary tumor growth in the hyperlipidemic estrogen-receptor positive E0771 breast cancer mouse model. Inhibition of autotaxin with the potent inhibitor PAT-505 did not attenuate breast cancer development in these hyperlipidemic mice. Further, replacing casein with amino acids or treatment with PAT-505 significantly reduced systemic markers of inflammation. ConclusionOur results show that casein is a significant source of PC when present in rodent diets. Diets formulated with amino acids in place of casein have higher proportion of circulating PC from the endogenous biosynthetic pool. Casein-containing high fat diets promote primary breast tumor development in mice through mechanisms that involve systemic inflammation but is independent of LPA production by autotaxin.

scholarly journals Chronic Dietary Branched-Chain Amino Acids Induced Lipid Oxidation and Blunted Insulin-Stimulated Glucose Production in Mice With NAFLD

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 529-529
Author(s):  
Chaitra Surugihalli ◽  
Vaishna Muralidaran ◽  
Kruti Patel ◽  
Tabitha Gregory ◽  
Nishanth Sunny
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Lipid Oxidation ◽  
Glucose Production ◽  
Branched Chain Amino Acids ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Branched Chain

Abstract Objectives Elevated circulating branched-chain amino acids (BCAAs) during insulin resistance are strong predictors of type 2 diabetes mellitus onset. Defects in BCAA degradation are evident in several tissues during insulin resistance and non-alcoholic fatty liver disease (NAFLD). Furthermore, alterations in BCAA metabolism are associated with changes in several aspects lipid metabolism, including lipogenesis, ketogenesis and mitochondrial TCA cycle activity. Considering the crosstalk between BCAAs and lipid metabolism, we hypothesized that chronic supplementation of BCAAs will modulate hepatic insulin resistance and mitochondrial lipid oxidation during NAFLD. Methods Mice (C57BL/6N) were reared on either a low-fat (LF; 10% fat kcal), high-fat (HF; 60% fat kcal or high-fat diet supplemented with BCAA (HFBA; 150% BCAA) for 24 weeks. Metabolic profiling was conducted under fed or overnight fasted (14–16 hrs) conditions. A subset of overnight fasted mice from the HF and HFBA groups were subjected to hyperinsulinemic euglycemic clamps, following implantation of jugular vein catheters. Results Feeding HF and HFBA diets resulted in NAFLD. Circulating BCAAs were higher in ‘fed’ mice consuming HFBA diet (e.g., Valine, µM ± SEM; 311 ± 38 in HF, 432 ± 34 in HFBA, P ≤ 0.05). Overnight fasting significantly reduced BCAA levels in all groups, but the fasting levels of BCAAs remained similar between groups. Fed-to-fasted fold changes in blood glucose, serum insulin and c-peptide were higher in HFBA mice (P ≤ 0.05). Insulin stimulated suppression of glucose production (% ± SEM; HF = 38 ± 11, HFBA = 16 ± 16) was blunted in HFBA mice.  Furthermore, fed-to-fasted expression of hepatic genes involved in lipid oxidation, including LCAD, MCAD, PPARa and CPT1a were significantly higher (P ≤ 0.05) in the HFBA mice. Conclusions In summary, chronic BCAA supplementation induced hepatic lipid oxidation gene expression, without any apparent improvements in insulin sensitivity. In conclusion, while the induction of lipid oxidation by BCAAs could explain certain beneficial effects associated with their supplementation, the longer-term impact of the BCAAs on insulin sensitivity need to be further explored. Funding Sources National Institutes of Health (NIH) grant RO1-DK-112865

Adipose tissue metabolism of obese mice on standard and high-fat diets

1961 ◽  
Vol 201 (1) ◽  
pp. 23-26 ◽  
Author(s):  
Serene Lochaya ◽  
Nicole Leboeuf ◽  
Jean Mayer ◽  
Bernard Leboeuf
Keyword(s):  
Adipose Tissue ◽  
Obese Mice ◽  
High Fat ◽  
Carbon Incorporation ◽  
Adipose Tissue Metabolism ◽  
Glucose Carbon ◽  
Low Carbohydrate ◽  
High Fat Diets ◽  
Fat Diets ◽  
Fat Feeding

Adipose tissue metabolism in vitro was studied, after substitution for several weeks of synthetic low-carbohydrate, high-fat (saturated or unsaturated) diets for the standard chow diet, in obese hyperglycemic mice and in their nonobese littermates. In tissue from nonobese mice fed the high-fat diets, glucose metabolism to CO2 and to fatty acids was diminished in the absence of added hormone, while glucose carbon incorporation to glyceride-glycerol was increased. Under insulin (0.1 unit/ml) stimulation, total glucose uptake was relatively decreased by the diets, as was glucose metabolism to CO2, to fatty acids, and to glycogen; however, glucose carbon incorporation to glyceride-glycerol was unaltered. Under epinephrine stimulation, the sum of glucose carbon recovery was less after high-fat feeding. No effect of high-fat feeding was detected on base-line rates of free fatty acid release nor on the effects of insulin or epinephrine on this process. No differences were found between the effects of saturated- or unsaturated-fat diets on any parameters. The metabolism of adipose tissue from obese mice was slightly, if at all, affected by high-fat feeding. These results are discussed in reference to the normal adaptation to low-carbohydrate, high-fat diets and to the metabolic abnormalities present in obese hyperglycemic mice.

scholarly journals The Combination of Mulberry Extracts and Silk Amino Acids Alleviated High Fat Diet-Induced Nonalcoholic Hepatic Steatosis by Improving Hepatic Insulin Signaling and Normalizing Gut Microbiome Dysbiosis in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Sunmin Park ◽  
Ting Zhang ◽  
Jing Yi Qiu ◽  
Xuangao Wu
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Disease Control ◽  
Normal Control ◽  
Insulin Signaling ◽  
High Fat ◽  
Hepatic Insulin Signaling ◽  
High Fat Diets ◽  
Fat Diets ◽  
Better Than

Mulberry water extracts (MB) and silk amino acids (SA) are reported to improve oxidative stress and inflammation, respectively. We hypothesized whether the mixture of mulberry water extracts and silk amino acids can alleviate nonalcoholic fatty liver disease (NAFLD) induced by high fat diets. Male Sprague Dawley rats were orally provided with high fat diets containing different ratios of MB and SA (1:3, MS1:3, or 1:5, MS1:5) or cellulose (the disease-control) for 12 weeks. Rats had 200 or 600 mg/kg bw of MS1:3 and MS1:5 (MS1:3-L, MS1:3-H; MS1:5-L, and MS1:5-H). Rats in the normal-control group were fed the 20% fat diet with cellulose. Disease-control rats exhibited much greater triglyceride (TG) deposition in the liver than the normal-control rats along with increased body weight gain, visceral fat mass, serum concentrations of cholesterol, triglyceride and nonesterified fatty acid (NEFA), and insulin resistance. Disease-control rats also had liver damage with increased oxidative stress and inflammation compared to the normal-control rats. MS1:3-H and MS1:5-H were found to have greater hepatic glycogen accumulation and decreased hepatic TG, insulin resistance, and dyslipidemia, with MS1:5-H being similar to the normal-control. MS1:3-H alleviated oxidative stress with lower hepatic lipid peroxide compared to MS1:5-H whereas MS1:5-H ameliorated inflammation and hepatocyte damage better than MS1:3-H. Both MS1:3-H and MS1:5-H potentiated hepatic insulin signaling (pAkt⟶pACC) and reduced the mRNA expression of TG synthesis genes mRNA (FAS and SREBP-1c). In the gut microbiome MS1:3-H elevated the ratio of Bacteroidales to Clostridiales in the cecum better than MS1:5-H but MS1:5-H reduced the proinflammatory Turicibacterales. In conclusion, both MS1:3-H and MS1:5-H prevented liver damage induced by high fat diets, mainly by suppressing oxidative stress and inflammation, respectively. MS1:3 and MS1:5 might be used as therapeutic agent for NAFLD.

scholarly journals Impaired Skeletal Muscle Branched-Chain Amino Acids Catabolism Contributes to Their Increased Circulating Levels in a Non-Obese Insulin-Resistant Fructose-Fed Rat Model

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 355 ◽  
Author(s):  
Jérémie David ◽  
Dominique Dardevet ◽  
Laurent Mosoni ◽  
Isabelle Savary-Auzeloux ◽  
Sergio Polakof
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Body Weight ◽  
Branched Chain Amino Acids ◽  
Laboratory Animals ◽  
Standard Diet ◽  
Elevated Blood ◽  
High Fat ◽  
Insulin Resistant ◽  
Branched Chain

Elevated plasma branched-chain amino acids (BCAA) levels are often observed in obese insulin-resistant (IR) subjects and laboratory animals. A reduced capacity of the adipose tissues (AT) to catabolize BCAA has been proposed as an explanation, but it seems restricted to obesity models of genetically modified or high fat–fed rodents. We aimed to determine if plasma BCAA levels were increased in a model of IR without obesity and to explore the underlying mechanisms. Rats were fed with a standard diet, containing either starch or fructose. BCAA levels, body weight and composition were recorded before and after 5, 12, 30, or 45 days of feeding. Elevated blood BCAA levels were observed in our IR model with unaltered body weight and composition. No changes were observed in the liver or the AT, but instead an impaired capacity of the skeletal muscle to catabolize BCAA was observed, including reduced capacity for transamination and oxidative deamination. Although the elevated blood BCAA levels in the fructose-fed rat seem to be a common feature of the IR phenotype observed in obese subjects and high fat–fed animals, the mechanisms involved in such a metabolic phenomenon are different, likely involving the skeletal muscle BCAA metabolism.

Branched-chain amino acids alleviate nonalcoholic steatohepatitis in rats

2013 ◽  
Vol 38 (8) ◽  
pp. 836-843 ◽  
Author(s):  
Tianrun Li ◽  
Leiluo Geng ◽  
Xin Chen ◽  
Miranda Miskowiec ◽  
Xuan Li ◽  
...  
Keyword(s):  
Amino Acids ◽  
Blood Flow ◽  
High Fat Diet ◽  
Plasma Lipid ◽  
Branched Chain Amino Acids ◽  
Fat Deposition ◽  
The Body ◽  
High Fat ◽  
Branched Chain ◽  
Rat Livers

Nonalcoholic steatohepatitis (NASH) is a prevalent disease in countries around the world. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine cannot be synthesized by the body and have been shown to promote muscle buildup; thus, it is logical to suggest that BCAAs can reduce fat deposition in the body. We used gonadectomized rats fed a high-fat diet to investigate the effects of BCAAs on lipid metabolism over an 8-week experimental period. Body composition, tissue histology, plasma lipid indices, and hormone levels were examined. We demonstrated that the body weights of rats were not significantly decreased but the mesenteric fat was significantly decreased (p < 0.05) in BCAA-treated rats. In addition, BCAAs decreased plasma lipid levels and fat deposition in the liver. At week 4, when the untreated rats displayed macrovesicular steatosis, BCAA-treated rats had only macrovesicular droplets in their hepatocytes. At week 8, when the untreated rat livers displayed profound inflammation and cirrhosis, BCAA-treated rat livers remained in the macrovesicular stage of steatosis. BCAAs induced higher blood glucose and plasma insulin levels (p < 0.05). BCAAs also improved liver blood flow by increasing mean arterial blood pressure and decreasing portal pressure, which helped delay the change in blood flow pattern to that of cirrhosis. BCAAs also induced the skeletal muscle to express higher levels of branched-chain α-keto acid dehydrogenase E1α, which indicates an enhanced metabolic capacity of BCAAs in muscle tissue. This study clearly demonstrates the effects of BCAAs on the amelioration of fat deposition in rats fed a high-fat diet.

Vigna nakashimae Extract Prevents Hepatic Steatosis in Obese Mice Fed High-Fat Diets

2014 ◽  
Vol 17 (12) ◽  
pp. 1322-1331 ◽  
Author(s):  
Yonghae Son ◽  
Min Kyung Jang ◽  
Myeong Ho Jung
Keyword(s):  
Hepatic Steatosis ◽  
Obese Mice ◽  
High Fat ◽  
High Fat Diets ◽  
Fat Diets

Metabolic Fate of Branched-Chain Amino Acids During Adipogenesis, in Adipocytes From Obese Mice and C2C12 Myotubes

2016 ◽  
Vol 118 (4) ◽  
pp. 808-818 ◽  
Author(s):  
Isabela Estrada-Alcalde ◽  
Miriam R. Tenorio-Guzman ◽  
Armando R. Tovar ◽  
Daniela Salinas-Rubio ◽  
Ivan Torre-Villalvazo ◽  
...  
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
C2c12 Myotubes ◽  
Obese Mice ◽  
Metabolic Fate ◽  
Branched Chain

scholarly journals Serum Metabolites Responding in a Dose-Dependent Manner to the Intake of a High-Fat Meal in Normal Weight Healthy Men Are Associated with Obesity

Metabolites ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 392
Author(s):  
Ueli Bütikofer ◽  
David Burnand ◽  
Reto Portmann ◽  
Carola Blaser ◽  
Flurina Schwander ◽  
...  
Keyword(s):  
Amino Acids ◽  
Branched Chain Amino Acids ◽  
Normal Weight ◽  
Dependent Manner ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Randomized Controlled ◽  
Two Factors ◽  
Branched Chain ◽  
Dose Dependent

Although the composition of the human blood metabolome is influenced both by the health status of the organism and its dietary behavior, the interaction between these two factors has been poorly characterized. This study makes use of a previously published randomized controlled crossover acute intervention to investigate whether the blood metabolome of 15 healthy normal weight (NW) and 17 obese (OB) men having ingested three doses (500, 1000, 1500 kcal) of a high-fat (HF) meal can be used to identify metabolites differentiating these two groups. Among the 1024 features showing a postprandial response, measured between 0 h and 6 h, in the NW group, 135 were dose-dependent. Among these 135 features, 52 had fasting values that were significantly different between NW and OB men, and, strikingly, they were all significantly higher in OB men. A subset of the 52 features was identified as amino acids (e.g., branched-chain amino acids) and amino acid derivatives. As the fasting concentration of most of these metabolites has already been associated with metabolic dysfunction, we propose that challenging normal weight healthy subjects with increasing caloric doses of test meals might allow for the identification of new fasting markers associated with obesity.

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