scholarly journals Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet

2009 ◽  
Vol 297 (2) ◽  
pp. G378-G384 ◽  
Author(s):  
Sean W. P. Koppe ◽  
Marc Elias ◽  
Richard H. Moseley ◽  
Richard M. Green
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Trans Fat ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
Trans Fats ◽  
Serum Alanine Aminotransferase ◽  
Triglyceride Content ◽  
In Trans ◽  
Fat Feeding

Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 ± 16 vs. 71 ± 7 U/l, P < 0.02) despite similar hepatic triglyceride content at each time point. Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1β (IL-1β) gene expression was 3.6-fold higher at 4 wk ( P < 0.05) and 5-fold higher at 8 wk ( P < 0.05) in trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1β levels compared with standard high-fat feeding.

High-fat diet-induced muscle insulin resistance: relationship to visceral fat mass

2000 ◽  
Vol 279 (6) ◽  
pp. R2057-R2065 ◽  
Author(s):  
Jong-Yeon Kim ◽  
Lorraine A. Nolte ◽  
Polly A. Hansen ◽  
Dong-Ho Han ◽  
Kevin Ferguson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fish Oil ◽  
Fat Mass ◽  
Visceral Fat ◽  
High Fat Diet ◽  
Corn Oil ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Visceral Fat Accumulation ◽  
Fat Feeding

It has been variously hypothesized that the insulin resistance induced in rodents by a high-fat diet is due to increased visceral fat accumulation, to an increase in muscle triglyceride (TG) content, or to an effect of diet composition. In this study we used a number of interventions: fish oil, leptin, caloric restriction, and shorter duration of fat feeding, to try to disassociate an increase in visceral fat from muscle insulin resistance. Substituting fish oil (18% of calories) for corn oil in the high-fat diet partially protected against both the increase in visceral fat and muscle insulin resistance without affecting muscle TG content. Injections of leptin during the last 4 days of a 4-wk period on the high-fat diet partially reversed the increase in visceral fat and the muscle insulin resistance, while completely normalizing muscle TG. Restricting intake of the high-fat diet to 75% of ad libitum completely prevented the increase in visceral fat and muscle insulin resistance. Maximally insulin-stimulated glucose transport was negatively correlated with visceral fat mass ( P < 0.001) in both the soleus and epitrochlearis muscles and with muscle TG concentration in the soleus ( P < 0.05) but not in the epitrochlearis. Thus we were unable to dissociate the increase in visceral fat from muscle insulin resistance using a variety of approaches. These results support the hypothesis that an increase in visceral fat is associated with development of muscle insulin resistance.

scholarly journals Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed High-Fat Diet

2020 ◽  
Author(s):  
Antu Antony ◽  
Zeqin Lian ◽  
Xiaoyuan Dai Perrard ◽  
Jerry Perrard ◽  
Hua Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Th2 Cells ◽  
High Fat ◽  
Interleukin 5 ◽  
Triglyceride Content ◽  
Metabolic Dysfunctions

<a>CD11c<sup>+</sup> macrophages/dendritic cells (MDCs) are increased and display classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed high-fat diet (HFD). Compared to littermate controls, cKO mice fed HFD (16 weeks) had reductions in MDC (mainly CD11c<sup>+</sup> macrophage) M1-like polarization and interferon-</a>g–expressing T helper type 1 (Th1) cells, but increases in interleukin-5–expressing Th2 cells and eosinophils in perigonadal and inguinal AT, and enhanced inguinal AT browning, with increased energy expenditure. cKO mice compared with controls also had significant reductions in triglyceride content in the liver and skeletal muscle and exhibited improved insulin sensitivity and glucose tolerance. Taken together, our results demonstrated that Stat1 in MDCs plays an important role in obesity-induced MDC M1-like polarization and AT inflammation and contributes to insulin resistance and metabolic dysfunctions in obese mice.

Beet (Beta vulgaris L.) Stalk and Leaf Supplementation Improves Glucose Homeostasis and Insulin Resistance Markers in Liver of Mice Exposed to a High-Fat Diet

2020 ◽  
Author(s):  
Isabela Micheletti Lorizola ◽  
Josiane Érica Miyamoto ◽  
Ana Luiza Figueiredo Vieira ◽  
Beatriz Rocchetti Sumere ◽  
Rosângela Maria Neves Bezerra ◽  
...  
Keyword(s):  
Beta Vulgaris ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Standard Diet ◽  
Hepatic Triglyceride ◽  
High Fat ◽  
Treatment Groups ◽  
Triglyceride Content ◽  
Resistance Markers ◽  
Unhealthy Diet

Abstract Background Although beet stalks and leaves are not consumed and are usually discarded, they are an important source of bioactive flavonoids possessing antioxidant and anti-inflammatory activity, which could be explored to prevent metabolic disorders associated with an unhealthy diet. The aim of this study was to assess the effect of supplementation with beet (Beta vulgaris L.) stalks and leaves on metabolic parameters and glucose homeostasis in mice exposed to a high-fat diet.Methods Six-week-old male Swiss mice were randomly divided into five experimental groups submitted to either standard diet (CT) or high-fat diet (HF), and HF-fed mice were subdivided into three treatment groups supplemented with oven-dehydrated beet stalks and leaves (SL), lyophilized beet stalks and leaves (Ly) or beet stalk and leaf extract (EX).Results Supplementation with SL was able to ameliorate glucose homeostasis (P < 0.05) with no alteration in hepatic triglyceride content. It remains to be clarified if the enhancement in the glucose homeostasis observed in HFSL could be a consequence of improvement in pancreatic insulin secretion and/or glucose uptake from skeletal muscle and white adipose tissues.Conclusions The current results suggest that beet stalks and leaves could be used as adjuvants to improve parameters related to glucose metabolism in the liver.

scholarly journals Myocardial insulin resistance induced by high fat feeding in heart failure is associated with preserved contractile function

2010 ◽  
Vol 299 (6) ◽  
pp. H1917-H1927 ◽  
Author(s):  
Bridgette A. Christopher ◽  
Hsuan-Ming Huang ◽  
Jessica M. Berthiaume ◽  
Tracy A. McElfresh ◽  
Xiaoqin Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Protein Expression ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Glucose Utilization ◽  
Contractile Function ◽  
High Fat ◽  
Myocardial Insulin Resistance ◽  
Fat Feeding

Previous studies have reported that high fat feeding in mild to moderate heart failure (HF) results in the preservation of contractile function. Recent evidence has suggested that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction, and insulin resistance is one potential mechanism for regulating substrate utilization. This study was designed to determine whether peripheral and myocardial insulin resistance exists with HF and/or a high-fat diet and whether myocardial insulin signaling was altered accordingly. Rats underwent coronary artery ligation (HF) or sham surgery and were randomized to normal chow (NC; 14% kcal from fat) or a high-fat diet (SAT; 60% kcal from fat) for 8 wk. HF + SAT animals showed preserved systolic (+dP/d t and stroke work) and diastolic (−dP/d t and time constant of relaxation) function compared with HF + NC animals. Glucose tolerance tests revealed peripheral insulin resistance in sham + SAT, HF + NC, and HF + SAT animals compared with sham + NC animals. PET imaging confirmed myocardial insulin resistance only in HF + SAT animals, with an uptake ratio of 2.3 ± 0.3 versus 4.6 ± 0.7, 4.3 ± 0.4, and 4.2 ± 0.6 in sham + NC, sham + SAT, and HF + NC animals, respectively; the myocardial glucose utilization rate was similarly decreased in HF + SAT animals only. Western blot analysis of insulin signaling protein expression was indicative of cardiac insulin resistance in HF + SAT animals. Specifically, alterations in Akt and glycogen synthase kinase-3β protein expression in HF + SAT animals compared with HF + NC animals may be involved in mediating myocardial insulin resistance. In conclusion, HF animals fed a high-saturated fat exhibited preserved myocardial contractile function, peripheral and myocardial insulin resistance, decreased myocardial glucose utilization rates, and alterations in cardiac insulin signaling. These results suggest that myocardial insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate HF.

scholarly journals Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed High-Fat Diet

2020 ◽  
Author(s):  
Antu Antony ◽  
Zeqin Lian ◽  
Xiaoyuan Dai Perrard ◽  
Jerry Perrard ◽  
Hua Liu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Th2 Cells ◽  
High Fat ◽  
Interleukin 5 ◽  
Triglyceride Content ◽  
Metabolic Dysfunctions

<a>CD11c<sup>+</sup> macrophages/dendritic cells (MDCs) are increased and display classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed high-fat diet (HFD). Compared to littermate controls, cKO mice fed HFD (16 weeks) had reductions in MDC (mainly CD11c<sup>+</sup> macrophage) M1-like polarization and interferon-</a>g–expressing T helper type 1 (Th1) cells, but increases in interleukin-5–expressing Th2 cells and eosinophils in perigonadal and inguinal AT, and enhanced inguinal AT browning, with increased energy expenditure. cKO mice compared with controls also had significant reductions in triglyceride content in the liver and skeletal muscle and exhibited improved insulin sensitivity and glucose tolerance. Taken together, our results demonstrated that Stat1 in MDCs plays an important role in obesity-induced MDC M1-like polarization and AT inflammation and contributes to insulin resistance and metabolic dysfunctions in obese mice.

Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1079-E1086 ◽  
Author(s):  
John W. Bullen ◽  
Susann Bluher ◽  
Theodoros Kelesidis ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Adiponectin Mrna ◽  
Obesity In Mice ◽  
Fat Feeding

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

scholarly journals Progressive adaptation of hepatic ketogenesis in mice fed a high-fat diet

2010 ◽  
Vol 298 (6) ◽  
pp. E1226-E1235 ◽  
Author(s):  
Nishanth E. Sunny ◽  
Santhosh Satapati ◽  
Xiaorong Fu ◽  
TianTeng He ◽  
Roshi Mehdibeigi ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Ketone Bodies ◽  
Fat Oxidation ◽  
Hepatic Insulin Resistance ◽  
High Fat ◽  
Peripheral Tissues ◽  
Insulin Resistant ◽  
Hepatic Fat ◽  
Fat Feeding

Hepatic ketogenesis provides a vital systemic fuel during fasting because ketone bodies are oxidized by most peripheral tissues and, unlike glucose, can be synthesized from fatty acids via mitochondrial β-oxidation. Since dysfunctional mitochondrial fat oxidation may be a cofactor in insulin-resistant tissue, the objective of this study was to determine whether diet-induced insulin resistance in mice results in impaired in vivo hepatic fat oxidation secondary to defects in ketogenesis. Ketone turnover (μmol/min) in the conscious and unrestrained mouse was responsive to induction and diminution of hepatic fat oxidation, as indicated by an eightfold rise during the fed (0.50+/−0.1)-to-fasted (3.8+/−0.2) transition and a dramatic blunting of fasting ketone turnover in PPARα−/− mice (1.0+/−0.1). C57BL/6 mice made obese and insulin resistant by high-fat feeding for 8 wk had normal expression of genes that regulate hepatic fat oxidation, whereas 16 wk on the diet induced expression of these genes and stimulated the function of hepatic mitochondrial fat oxidation, as indicated by a 40% induction of fasting ketogenesis and a twofold rise in short-chain acylcarnitines. Together, these findings indicate a progressive adaptation of hepatic ketogenesis during high-fat feeding, resulting in increased hepatic fat oxidation after 16 wk of a high-fat diet. We conclude that mitochondrial fat oxidation is stimulated rather than impaired during the initiation of hepatic insulin resistance in mice.

scholarly journals TRPM2 Ca2+ channel regulates energy balance and glucose metabolism

2012 ◽  
Vol 302 (7) ◽  
pp. E807-E816 ◽  
Author(s):  
Zhiyou Zhang ◽  
Wenyi Zhang ◽  
Dae Young Jung ◽  
Hwi Jin Ko ◽  
Yongjin Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Gsk 3Β ◽  
Fat Feeding

TRPM2 Ca2+-permeable cation channel is widely expressed and activated by markers of cellular stress. Since inflammation and stress play a major role in insulin resistance, we examined the role of TRPM2 Ca2+ channel in glucose metabolism. A 2-h hyperinsulinemic euglycemic clamp was performed in TRPM2-deficient (KO) and wild-type mice to assess insulin sensitivity. To examine the effects of diet-induced obesity, mice were fed a high-fat diet for 4–10 mo, and metabolic cage and clamp studies were conducted in conscious mice. TRPM2-KO mice were more insulin sensitive partly because of increased glucose metabolism in peripheral organs. After 4 mo of high-fat feeding, TRPM2-KO mice were resistant to diet-induced obesity, and this was associated with increased energy expenditure and elevated expressions of PGC-1α, PGC-1β, PPARα, ERRα, TFAM, and MCAD in white adipose tissue. Hyperinsulinemic euglycemic clamps showed that TRPM2-KO mice were more insulin sensitive, with increased Akt and GSK-3β phosphorylation in heart. Obesity-mediated inflammation in adipose tissue and liver was attenuated in TRPM2-KO mice. Overall, TRPM2 deletion protected mice from developing diet-induced obesity and insulin resistance. Our findings identify a novel role of TRPM2 Ca2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.

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