Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of essential hypertension increases with obesity; however, the mechanisms that link obesity with hypertension are unclear. Renal cytochrome P450 (CYP)-derived eicosanoids--hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs)--have been shown to play an important role in the regulation of renal function, vascular tone, and blood pressure. The objective of this study was to examine CYP-derived eicosanoid synthesis in the different renal zones (cortex, medulla, and papilla) of rats fed a high fat diet (HF). Male Sprague-Dawley rats were fed a HF diet or regular rat chow for 10 weeks. After 10 weeks, HF rats showed significantly higher systolic blood pressure, body weight, and fat:body weight ratio. The renal omega-hydroxylase activity was decreased by 46% in cortex, 43% in medulla, and 46% in papilla of HF rats. The renal epoxygenase activity was decreased by 46% in cortex, 31% in medulla, and 56% in papilla of HF rats. Interestingly, the changes in the rate of 20-HETE and EET formation in different renal zones were consistent with the levels of expression of CYP4A and CYP2C23 proteins, respectively. Furthermore, there were no significant changes in the synthesis of these metabolites in the renal microvessels. These results demonstrate that HF diet causes the downregulation of CYP4A and CYP2C23 in renal tubules, and these proteins are responsible for renal 20-HETE and EET formation. The reduction in the synthesis of these eicosanoids may play an important role in the regulation of renal function and blood pressure in obesity-induced hypertension.
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PMID:Downregulation of renal CYP-derived eicosanoid synthesis in rats with diet-induced hypertension. 1293 36

Fatty liver disease is a common lipid metabolism disorder influenced by the combination of individual genetic makeup, drug exposure, and life-style choices that are frequently associated with metabolic syndrome, which encompasses obesity, dyslipidemia, hypertension, hypertriglyceridemia, and insulin resistant diabetes. Common to obesity related dyslipidemia is the excessive storage of hepatic fatty acids (steatosis), due to a decrease in mitochondria beta-oxidation with an increase in both peroxisomal beta-oxidation, and microsomal omega-oxidation of fatty acids through peroxisome proliferator activated receptors (PPARs). How steatosis increases PPARalpha activated gene expression of fatty acid transport proteins, peroxisomal and mitochondrial fatty acid beta-oxidation and omega-oxidation of fatty acids genes regardless of whether dietary fatty acids are polyunsaturated (PUFA), monounsaturated (MUFA), or saturated (SFA) may be determined by the interplay of PPARs and HNF4alpha with the fatty acid transport proteins L-FABP and ACBP. In hepatic steatosis and steatohepatitis, the omega-oxidation cytochrome P450 CYP4A gene expression is increased even with reduced hepatic levels of PPARalpha. Although numerous studies have suggested the role ethanol-inducible CYP2E1 in contributing to increased oxidative stress, Cyp2e1-null mice still develop steatohepatitis with a dramatic increase in CYP4A gene expression. This strongly implies that CYP4A fatty acid omega-hydroxylase P450s may play an important role in the development of steatohepatitis. In this review and tutorial, we briefly describe how fatty acids are partitioned by fatty acid transport proteins to either anabolic or catabolic pathways regulated by PPARs, and we explore how medium-chain fatty acid (MCFA) CYP4A and long-chain fatty acid (LCFA) CYP4Fomega-hydroxylase genes are regulated in fatty liver. We finally propose a hypothesis that increased CYP4A expression with a decrease in CYP4F genes may promote the progression of steatosis to steatohepatitis.
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PMID:PPAR/RXR Regulation of Fatty Acid Metabolism and Fatty Acid omega-Hydroxylase (CYP4) Isozymes: Implications for Prevention of Lipotoxicity in Fatty Liver Disease. 2030 Apr 78

Altered regulation of vitamin D metabolites, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D (1,25[OH]2D), was observed in high-fat diet (HFD)-induced obesity. We hypothesized that these HFD-induced changes in vitamin D metabolism would be reversed by decreasing fat mass through dietary intervention. Four-week-old C57BL/6J mice were assigned to 1 of 3 experimental diet groups: (1) the LL group was fed a control diet for 31 weeks, (2) the HH group was fed an HFD for 31 weeks, and (3) the HL group was fed HFD for 15 weeks then switched to the control diet for the remaining 16 weeks. The fat mass of the HL group decreased by 15% from the 14th to the 30th week. Serum 1,25(OH)2D level was significantly higher in the HH group than the LL group, whereas that of the HL group was intermediate to the 2 groups. Serum parathyroid hormone and renal 1-hydroxylase (Cyp27b1) mRNA levels, which are known to stimulate renal 1,25(OH)2D production, were significantly higher in the HH group than the LL group. After losing fat mass, the HL group had significantly lower renal Cyp27b1 mRNA levels than the HH group. No differences were found in serum 25-hydroxyvitamin D levels and mRNA levels of hepatic 25-hydroxylases. In adipose tissue, mRNA levels of 25-hydroxylase and vitamin D receptor were elevated in parallel to the adiposity. In conclusion, serum 1,25(OH)2D levels were closely associated with body adiposity, and reducing fat mass by changing to a lower-fat diet can reverse this obesity-associated increase in circulating 1,25(OH)2D levels.
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PMID:Dysregulated 1,25-dihydroxyvitamin D levels in high-fat diet-induced obesity can be restored by changing to a lower-fat diet in mice. 2968 23