ABNORMAL P85/P110 TYPE PI-KINASE ACTIVATION IN ZUCKER FATTY RATS AND HIGH-FAT FED RATS

2002 ◽  
pp. 349-370
Keyword(s):  
High Fat ◽  
Kinase Activation ◽  
Pi Kinase

scholarly journals AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

2019 ◽  
Vol 60 (5) ◽  
pp. 937-952 ◽  
Author(s):  
Anne-Emilie Declèves ◽  
Anna V. Mathew ◽  
Aaron M. Armando ◽  
Xianlin Han ◽  
Edward A. Dennis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kidney Disease ◽  
Ampk Activation ◽  
High Fat ◽  
Kinase Activation ◽  
Venous Circulation ◽  
Protein Kinase Activation ◽  
Anti Inflammatory ◽  
Amp Activated Protein Kinase

High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMP-activated protein kinase (AMPK) activation. Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative MS to determine PUFA and eicosanoid content in kidneys, urine, and renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free pro-inflammatory arachidonic acid (AA) and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA- and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPA-derived LOX and NE metabolites decreased. Conversely, treatment with 5-aminoimidazole-4-carboxamide-1-β-D-furanosyl 5′-monophosphate (AICAR), an AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, kidney and circulating AA, AA metabolites, EPA-derived LOX, and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro- and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

scholarly journals Inhibitory Effects ofChung Hun Wha Dam Tang(CHWDT) on High-Fat Diet-Induced Obesity via AMP-Activated Protein Kinase Activation

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Md. Jamal Uddin ◽  
Yeonsoo Joe ◽  
Min Zheng ◽  
Sena Kim ◽  
Hoyoung Lee ◽  
...  
Keyword(s):  
High Fat Diet ◽  
No Production ◽  
Mice Model ◽  
Inhibitory Effects ◽  
High Fat ◽  
Kinase Activation ◽  
Raw264.7 Macrophages ◽  
Protein Kinase Activation

TheChung Hun Wha Dam Tang(CHWDT) herbal combination was reported to cease dizziness and phlegm. However, the effect of CHWDT in obesity has not yet been known mechanically. Therefore, we investigated whether this CHWDT could protect the cells from lipogenesis, gluconeogenesis, and inflammation in both in vivo and in vitro. CHWDT significantly decreased body weight, epididymal and perirenal fat content without affecting feed intake in high-fat diet-induced obese mice model. Additionally, CHWDT inhibited obesity-induced SREBP1, FAS, PGC1α, G6Pase, PEPCK and increased CPT1, ACO, and LCAD genes expression in vivo and in vitro. Proinflammatory cytokines like TNF-αand iNOS expression were reduced by CHWDT in both Raw264.7 macrophages and HepG2 cells. In addition, NO production was also significantly decreased by CHWDT in LPS-stimulated macrophages. Furthermore, AMPKαactivation by CHWDT was involved in inhibition of obesity by reducing triglycerides production and increasing CPT1 expression. Based on all of the results, we suggest that CHWDT has inhibitory effects on obesity-induced lipogenesis, gluconeogenesis, and inflammation via AMPKαactivation.

scholarly journals Loss of CTRP1 disrupts glucose and lipid homeostasis

2016 ◽  
Vol 311 (4) ◽  
pp. E678-E697 ◽  
Author(s):  
Susana Rodriguez ◽  
Xia Lei ◽  
Pia S. Petersen ◽  
Stefanie Y. Tan ◽  
Hannah C. Little ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Lipid Synthesis ◽  
High Fat ◽  
Kinase Activation ◽  
Cholesterol Levels ◽  
Protein Kinase Activation ◽  
Amp Activated Protein Kinase

C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis. Impaired glucose metabolism in Ctrp1 KO mice was associated with increased hepatic gluconeogenic gene expression and decreased skeletal muscle glucose transporter glucose transporter 4 levels and AMP-activated protein kinase activation. Loss of CTRP1 enhanced the clearance of orally administered lipids but did not affect intestinal lipid absorption, hepatic VLDL-triglyceride export, or lipoprotein lipase activity. In contrast to triglycerides, hepatic cholesterol levels were reduced in Ctrp1 KO mice, paralleling the reduced expression of cholesterol synthesis genes. Contrary to expectations, when challenged with a high-fat diet to induce obesity, Ctrp1 KO mice had increased physical activity and reduced body weight, adiposity, and expression of lipid synthesis and fibrotic genes in adipose tissue; these phenotypes were linked to elevated FGF-21 levels. Due in part to increased hepatic AMP-activated protein kinase activation and reduced expression of lipid synthesis genes, Ctrp1 KO mice fed a high-fat diet also had reduced liver and serum triglyceride and cholesterol levels. Taken together, these results provide genetic evidence to establish the significance of CTRP1 to systemic energy metabolism in different metabolic and dietary contexts.

scholarly journals Novel mitochondrial complex I inhibitors restore glucose-handling abilities of high-fat fed mice

2016 ◽  
Vol 56 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Darren S D Martin ◽  
Siobhán Leonard ◽  
Robert Devine ◽  
Clara Redondo ◽  
Gemma K Kinsella ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
High Fat Diet ◽  
Complex I ◽  
Cellular Level ◽  
High Fat ◽  
Insulin Sensitizer ◽  
Kinase Activation ◽  
Drug Of Choice ◽  
Protein Kinase Activation ◽  
Complex I Activity

Metformin is the main drug of choice for treating type 2 diabetes, yet the therapeutic regimens and side effects of the compound are all undesirable and can lead to reduced compliance. The aim of this study was to elucidate the mechanism of action of two novel compounds which improved glucose handling and weight gain in mice on a high-fat diet. Wildtype C57Bl/6 male mice were fed on a high-fat diet and treated with novel, anti-diabetic compounds. Both compounds restored the glucose handling ability of these mice. At a cellular level, these compounds achieve this by inhibiting complex I activity in mitochondria, leading to AMP-activated protein kinase activation and subsequent increased glucose uptake by the cells, as measured in the mouse C2C12 muscle cell line. Based on the inhibition of NADH dehydrogenase (IC50 27µmolL−1), one of these compounds is close to a thousand fold more potent than metformin. There are no indications of off target effects. The compounds have the potential to have a greater anti-diabetic effect at a lower dose than metformin and may represent a new anti-diabetic compound class. The mechanism of action appears not to be as an insulin sensitizer but rather as an insulin substitute.

scholarly journals Increased Apoptosis in High-Fat Diet–Induced Nonalcoholic Steatohepatitis in Rats Is Associated with c-Jun NH2-Terminal Kinase Activation and Elevated Proapoptotic Bax

2008 ◽  
Vol 138 (10) ◽  
pp. 1866-1871 ◽  
Author(s):  
Yan Wang ◽  
Lynne M. Ausman ◽  
Robert M. Russell ◽  
Andrew S. Greenberg ◽  
Xiang-Dong Wang
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
High Fat ◽  
Kinase Activation
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