scholarly journals Effects of DGAT1 deficiency on energy and glucose metabolism are independent of adiponectin

2006 ◽  
Vol 291 (2) ◽  
pp. E388-E394 ◽  
Author(s):  
Ryan S. Streeper ◽  
Suneil K. Koliwad ◽  
Claudio J. Villanueva ◽  
Robert V. Farese
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
Glucose And Lipid Metabolism ◽  
Diet Induced Obesity ◽  
Triacylglycerol Synthesis ◽  
Triacylglycerol Accumulation ◽  
Hepatic Triacylglycerol ◽  
Deficient Mice

Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin sensitivity and are protected from obesity, a result of increased energy expenditure. In these mice, factors derived from white adipose tissue (WAT) contribute to the systemic changes in metabolism. One such factor, adiponectin, increases fatty acid oxidation and enhances insulin sensitivity. To test the hypothesis that adiponectin is required for the altered energy and glucose metabolism in DGAT1-deficient mice, we generated adiponectin-deficient mice and introduced adiponectin deficiency into DGAT1-deficient mice by genetic crosses. Although adiponectin-deficient mice fed a high-fat diet were heavier, exhibited worse glucose tolerance, and had more hepatic triacylglycerol accumulation than wild-type controls, mice lacking both DGAT1 and adiponectin, like DGAT1-deficient mice, were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis. These findings indicate that adiponectin is required for normal energy, glucose, and lipid metabolism but that the metabolic changes induced by DGAT1-deficient WAT are independent of adiponectin and are likely due to other WAT-derived factors. Our findings also suggest that the pharmacological inhibition of DGAT1 may be useful for treating human obesity and insulin resistance associated with low circulating adiponectin levels.

Krill oil and xanthigen separately inhibit high fat diet induced obesity and hepatic triacylglycerol accumulation in mice

2015 ◽  
Vol 19 ◽  
pp. 913-921 ◽  
Author(s):  
Ming-Fen Lee ◽  
Ching-Shu Lai ◽  
An-Chin Cheng ◽  
Jain-Sin Hou ◽  
Vladimir Badmaev ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Krill Oil ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Triacylglycerol Accumulation ◽  
Hepatic Triacylglycerol

scholarly journals IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

2015 ◽  
Vol 309 (8) ◽  
pp. R835-R844 ◽  
Author(s):  
Emanuele Loro ◽  
Erin L. Seifert ◽  
Cynthia Moffat ◽  
Freddy Romero ◽  
Manoj K. Mishra ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Wide Distribution ◽  
Liver Fat ◽  
Acid Oxidation ◽  
Direct Effects ◽  
High Fat ◽  
Binding Partner ◽  
Insulin Resistant ◽  
Diet Induced Obesity

IL-15Rα is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15Rα take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15Rα promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15Rα on metabolism and obesity are currently unknown. We report that mice lacking IL-15Rα (IL-15Rα−/−) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15Rα−/− mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15Rα−/− are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15Rα in metabolism and obesity.

Abstract 437: Increasing Cardiac Fatty Acid Oxidation Protects Against High Fat Diet Induced Cardiomyopathy in Mice

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Dan Shao ◽  
Nathan Roe ◽  
Loreta D Tomasi ◽  
Alyssa N Braun ◽  
Ana Mattos ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Cardiac Dysfunction ◽  
High Fat Diet ◽  
Heart Weight ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Cardiac Lipotoxicity

In the obese and diabetic heart, an imbalance between fatty acid uptake and fatty acid oxidation (FAO) promotes the development of cardiac lipotoxicity. We previously showed that cardiac specific deletion of acetyl CoA carboxylase 2 (ACC2) was effective in increasing myocardial FAO while maintaining normal cardiac function and energetics. In this study, we tested the hypothesis that ACC2 deletion in an adult heart would prevent the cardiac lipotoxic phenotype in a mouse model of diet-induced obesity. ACC2 flox/flox (CON) and ACC2 flox/flox-MerCreMer+ (iKO) after tamoxifen injection were subjected to a high fat diet (HFD) for 24 weeks. HFD induced similar body weight gain and glucose intolerance in CON and iKO. In isolated Langendorff-perfused heart experiments, HFD feeding increased FAO 1.6-fold in CON mice which was increased to 2.5-fold in iKO mice compared with CON on chow diet. Fractional shortening was significantly decreased in CON-HFD (32.8±2.8% vs. 39.2±3.2%, p< 0.05, n=5-6), but preserved in iKO-HFD mice (42.8±2.3%, vs. 38.5±1.4%, n=6), compared to respective chow fed controls. Diastolic function, assessed by E’/A’ ratio using tissue Doppler imaging, was significantly decreased in CON-HFD mice (1.11±0.08 vs. 0.91±0.09, p<0.05 n=5-6), while no difference was observed in iKO-HFD compared to iKO-chow (1.10±0.03 vs. 1.09±0.04, n=6). Heart weight /Tibia length ratio was significantly higher in CON than iKO mice after HFD feeding (7.19±0.22 vs. 6.47±0.28, p<0.05, n=6). Furthermore, HFD induced mitochondria super complex II, III and V instability, which was attenuated in iKO-HFD mice. These data indicate that elevated myocardial FAO per se does not cause the development of cardiac dysfunction in obese animals. In fact, enhancing FAO via ACC2 deletion prevents HFD induced cardiac dysfunction and attenuates pathological hypertrophy. These effects may be mediated, in part, by maintenance of mitochondrial integrity. Taken together, our findings suggest that promoting cardiac FAO is an effective strategy to resist the development of cardiac lipotoxicity during diet-induced obesity.

scholarly journals Increased Insulin Sensitivity by High-Altitude Hypoxia in Mice with High-Fat Diet-Induced Obesity Is Associated with Activated AMPK Signaling and Subsequently Enhanced Mitochondrial Biogenesis in Skeletal Muscles

Obesity Facts ◽  
2020 ◽  
Vol 13 (5) ◽  
pp. 455-472
Author(s):  
Kang Song ◽  
Yifan Zhang ◽  
Qin Ga ◽  
Zhenzhong Bai ◽  
Ri-Li Ge
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Protein Kinase ◽  
High Altitude ◽  
Mitochondrial Biogenesis ◽  
High Fat Diet ◽  
Skeletal Muscles ◽  
Acid Oxidation ◽  
High Fat ◽  
Low Altitude

<b><i>Background:</i></b> This study aimed to investigate whether and how high altitude-associated ambient hypoxia affects insulin sensitivity in mice fed a high-fat diet (HFD). <b><i>Methods:</i></b> Mice were randomly divided into a control group (with normal diet feeding and low-altitude housing), LA/HFD group (with HFD feeding and low-altitude housing), and HA/HFD group (with HFD feeding and high-altitude housing). <b><i>Results:</i></b> After 8 weeks, mice in the HA/HFD group showed improved insulin sensitivity-related indices compared with the LA/HFD group. In mice residing in a low-altitude region, HFD significantly impaired mitochondrial respiratory function and mitochondrial DNA content in skeletal muscles, which was partially reversed in mice in the HA/HFD group. In addition, the fatty acid oxidation-related enzyme gene <i>CPT1</i> (carnitine palmitoyltransferase 1) and genes related to mitochondrial biogenesis such as peroxisome proliferator-activated receptor-γ coactivator-1α (<i>PGC-1α</i>), nuclear respiratory factor 1 (<i>NRF1</i>), and mitochondrial transcription factor A (<i>Tfam</i>) were upregulated in the skeletal muscles of mice housed at high altitude, in comparison to in the LA/HFD group. Furthermore, AMPK (adenosine monophosphate-activated protein kinase) signaling was activated in the skeletal muscles, as evidenced by a higher expression of phosphorylated AMPK (p-AMPK) and protein kinase B (p-AKT) in the HA/HFD group than in the LA/HFD group. <b><i>Conclusion:</i></b> Our study suggests that high-altitude hypoxia improves insulin sensitivity in mice fed an HFD, which is associated with AMPK activation in the skeletal muscle and consequently enhanced mitochondrial biogenesis and fatty acid oxidation. This work provides a molecular explanation for why high altitude is associated with a reduced incidence of insulin resistance in the obese population.

RS4-type resistant starch prevents high-fat diet-induced obesity via increased hepatic fatty acid oxidation and decreased postprandial GIP in C57BL/6J mice

2010 ◽  
Vol 298 (3) ◽  
pp. E652-E662 ◽  
Author(s):  
Akira Shimotoyodome ◽  
Junko Suzuki ◽  
Daisuke Fukuoka ◽  
Ichiro Tokimitsu ◽  
Tadashi Hase
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Resistant Starch ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Fat Utilization ◽  
Hepatic Fatty Acid ◽  
Diet Induced Obesity ◽  
Hepatic Fatty Acid Oxidation

Chemically modified starches (CMS) are RS4-type resistant starch, which shows a reduced availability, as well as high-amylose corn starch (HACS, RS2 type), compared with the corresponding unmodified starch. Previous studies have shown that RS4 increases fecal excretion of bile acids and reduces zinc and iron absorption in rats. The aim of this study was to investigate the effects of dietary RS4 supplementation on the development of diet-induced obesity in mice. Weight- and age-matched male C57BL/6J mice were fed for 24 wk on a high-fat diet containing unmodified starch, hydroxypropylated distarch phosphate (RS4), or HACS (RS2). Those fed the RS4 diet had significantly lower body weight and visceral fat weight than those fed either unmodified starch or the RS2 diet. Those fed the RS4 diet for 4 wk had a significantly higher hepatic fatty acid oxidation capacity and related gene expression and lower blood insulin than those fed either unmodified starch or the RS2 diet. Indirect calorimetry showed that the RS4 group exhibited higher energy expenditure and fat utilization compared with the RS2 group. When gavaged with fat (trioleate), RS4 stimulated a lower postprandial glucose-dependent insulinotropic polypeptide (GIP; incretin) response than RS2. Higher blood GIP levels induced by chronic GIP administration reduced fat utilization in high-fat diet-fed mice. In conclusion, dietary supplementation with RS4-type resistant starch attenuates high-fat diet-induced obesity more effectively than RS2 in C57BL/6J mice, which may be attributable to lower postprandial GIP and increased fat catabolism in the liver.

scholarly journals Effects of retinoid therapy on insulin sensitivity, lipid profile and circulating adipocytokines

2006 ◽  
Vol 154 (1) ◽  
pp. 83-86 ◽  
Author(s):  
S Corbetta ◽  
R Angioni ◽  
A Cattaneo ◽  
P Beck-Peccoz ◽  
A Spada
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Lipid Profile ◽  
Oral Treatment ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Glucose And Lipid Metabolism ◽  
Cholesterol Levels

Objective: In vitro and in vivo models indicate that all-trans retinoic acids influence glucose and lipid metabolism. We aimed to evaluate the effects of chronic treatment with acitretin, an all-trans retinoic acid, on glucose metabolism, lipid profile and adiponectin and resistin levels. Design: Ten normoglycemic, normolipemic patients affected with psoriasis vulgaris were studied before and after 1 and 3 months of oral treatment with 35 μg of acitretin. Methods: Glucose metabolism, lipid profile, and adiponectin and resistin levels were evaluated in basal conditions and after acitretin treatment. Ten healthy subjects matched for age, body mass index (BMI) and insulin sensitivity were studied as controls. Results: One-month acitretin treatment reduced psoriasis activity, insulin sensitivity, evaluated as QUICKI values (0.364 ± 0.034 versus 0.329 ± 0.051; P < 0.05) and HOMA-IR index (1.53 ± 0.73 versus 2.59 ± 1.41; P < 0.05), and high-density lipoprotein (HDL)-cholesterol levels (45.2 ± 11.7 versus 39.4 ± 10.4 mg/dl; P = 0.01). The impairment in glucose and lipid homeostasis was transient and not associated to BMI variations. Adiponectin levels did not change during the treatment, while resistin levels, which were higher in untreated patients than in controls (9.4 ± 4.4 versus 6.2 ± 2.1 ng/ml; P = 0.05), fell within the normal range after 1 and 3 months of therapy. The normalization of resistin levels occurred without significant changes in circulating tumor necrosis factor α (TNFα) levels, which persisted elevated throughout the treatment. Conclusions: Treatment with a low dose of acitretin induced a mild, transient reduction of insulin sensitivity and HDL-cholesterol levels that was not related to modifications of adiponectin, resistin and TNFα levels. Although the role of resistin in humans remains elusive, the levels of this adipocytokine seem to be affected, at least in part, by retinoids.

scholarly journals Increasing Adipocyte Lipoprotein Lipase Improves Glucose Metabolism in High Fat Diet-induced Obesity

2015 ◽  
Vol 290 (18) ◽  
pp. 11547-11556 ◽  
Author(s):  
R. Grace Walton ◽  
Beibei Zhu ◽  
Resat Unal ◽  
Michael Spencer ◽  
Manjula Sunkara ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Lipoprotein Lipase ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity

scholarly journals Shift in metabolic fuel in acylation-stimulating protein-deficient mice following a high-fat diet

2008 ◽  
Vol 294 (6) ◽  
pp. E1051-E1059 ◽  
Author(s):  
Christian Roy ◽  
Sabina Paglialunga ◽  
Alexandre Fisette ◽  
Patrick Schrauwen ◽  
Esther Moonen-Kornips ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Ex Vivo ◽  
Direct Result ◽  
Acid Oxidation ◽  
High Fat ◽  
Metabolic Potential ◽  
Deficient Mice

ASP-deficient mice (C3 KO) have delayed postprandial TG clearance, are hyperphagic, and display increased energy expenditure. Markers of carbohydrate and fatty acid metabolism in the skeletal muscle and heart were examined to evaluate the mechanism. On a high-fat diet, compared with wild-type mice, C3 KO mice have increased energy expenditure, decreased RQ, lower ex vivo glucose oxidation (−39%, P = 0.018), and higher ex vivo fatty acid oxidation (+68%, P = 0.019). They have lower muscle glycogen content (−25%, P < 0.05) and lower activities for the glycolytic enzymes glycogen phosphorylase (−31%, P = 0.005), hexokinase (−43%, P = 0.007), phosphofructokinase (−51%, P < 0.0001), and GAPDH (−15%, P = 0.04). Analysis of mitochondrial enzyme activities revealed that hydroxyacyl-coenzyme A dehydrogenase was higher (+25%, P = 0.004) in C3 KO mice. Furthermore, Western blot analysis of muscle revealed significantly higher fatty acid transporter CD36 (+40%, P = 0.006) and cytochrome c (a marker of mitochondrial content; +69%, P = 0.034) levels in C3 KO mice, whereas the activity of AMP kinase was lower (−48%, P = 0.003). Overall, these results demonstrate a shift in the metabolic potential of skeletal muscle toward increased fatty acid utilization. Whether this is 1) a consequence of decreased adipose tissue storage with repartitioning toward muscle or 2) a direct result of the absence of ASP interaction with the receptor C5L2 in muscle remains to be determined. However, these in vivo data suggest that ASP inhibition could be a potentially viable approach in correcting muscle metabolic dysfunction in obesity.

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