Hepatic Adenosine Triphosphate Reduction Through the Short‐Chain Fatty Acids–Peroxisome Proliferator‐Activated Receptor γ–Uncoupling Protein 2 Axis Alleviates Immune‐Mediated Acute Hepatitis in Inulin‐Supplemented Mice

Objective. To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods. Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n=198) and abnormal glucose tolerance group (n=358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results. The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P=0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P=0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P=0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P=0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion. It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

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Role of Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α in the Transcriptional Regulation of the Human Uncoupling Protein 2 Gene in INS-1E Cells

Endocrinology ◽

10.1210/en.2005-0817 ◽

2006 ◽

Vol 147 (2) ◽

pp. 966-976 ◽

Cited By ~ 42

Author(s):

Hannes Oberkofler ◽

Kerstin Klein ◽

Thomas K. Felder ◽

Franz Krempler ◽

Wolfgang Patsch

Keyword(s):

Transcriptional Regulation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

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The Effect of Short-chain Fatty Acid Supplementation on Acute Colonic Inflammation in Rats Fed With Western Diet: Role of the Peroxisome Proliferator-activated Receptor-gamma

10.21203/rs.3.rs-1067920/v1 ◽

2021 ◽

Author(s):

Mustafa Sevim ◽

Çiğdem Çantalı-Öztürk ◽

Ali Mergen ◽

Eda Ceren Güllü ◽

Elif Yaren Ayvaz ◽

...

Keyword(s):

Oxidative Damage ◽

Lipid Profile ◽

Short Chain Fatty Acids ◽

Normal Diet ◽

Short Chain ◽

Albino Rats ◽

Peroxisome Proliferator ◽

Protective Effects ◽

Colonic Inflammation ◽

Peroxisome Proliferator Activated Receptor

Abstract Increased incidence of inflammatory bowel disease (IBD) is associated with the consumption of westernized diet (WD). In male Wistar albino rats induced with colitis by oral intake of dextran-sulfate sodium (DSS) for 10 days, we investigated how colitis-induced oxidative damage is affected by WD consumption started 3 weeks before DSS intake. Secondly, the putative protective effects of short-chain fatty acids (SCFAs) were evaluated in both WD-fed and normal diet (ND)-fed rats. WD consumption prior to colitis induction alleviated oxidative damage and suppressed inflammatory response of the colon via the modulation of peroxisome proliferator-activated receptor (PPAR)-γ activity, suggesting a preconditioning impact of the WD. Moreover, addition of SCFA to WD abolished the elevations in lipid profile, while SCFA added to either ND or WD during the 10-day development of colonic inflammation depressed the pro-inflammatory TNF-α and IL-6 expressions and upregulated IL-10, but the reduction in oxidative damage due to WD was not further changed. The results demonstrated that acute colonic inflammation is alleviated when it is preceded by the consumption of WD, and SCFAs improved WD-induced disruption in lipid profile, implicating that SCFAs would be advantageous in IBD patients comorbid with metabolic syndrome.

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Developmental and Tissue-Specific Involvement of Peroxisome Proliferator-Activated Receptor-α in the Control of Mouse Uncoupling Protein-3 Gene Expression

Endocrinology ◽

10.1210/en.2006-0226 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4695-4704 ◽

Cited By ~ 14

Author(s):

Neus Pedraza ◽

Meritxell Rosell ◽

Joan Villarroya ◽

Roser Iglesias ◽

Frank J. Gonzalez ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Fatty Acids ◽

Fatty Acid ◽

Mrna Expression ◽

Uncoupling Protein ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Ucp3 Gene ◽

Uncoupling Protein 3

Uncoupling protein-3 (UCP3) is a member of the mitochondrial carrier family expressed preferentially in skeletal muscle and heart. It appears to be involved in metabolic handling of fatty acids in a way that minimizes excessive production of reactive oxygen species. Fatty acids are powerful regulators of UCP3 gene transcription. We have found that the role of peroxisome proliferator-activated receptor-α (PPARα) on the control of UCP3 gene expression depends on the tissue and developmental stage. In adults, UCP3 mRNA expression is unaltered in skeletal muscle from PPARα-null mice both in basal conditions and under the stimulus of starvation. In contrast, UCP3 mRNA is down-regulated in adult heart both in fed and fasted PPARα-null mice. This occurs despite the increased levels of free fatty acids caused by fasting in PPARα-null mice. In neonates, PPARα-null mice show impaired UCP3 mRNA expression in skeletal muscle in response to milk intake, and this is not a result of reduced free fatty acid levels. The murine UCP3 promoter is activated by fatty acids through either PPARα or PPARδ but not by PPARγ or retinoid X receptor alone. PPARδ-dependent activation could be a potential compensatory mechanism to ensure appropriate expression of UCP3 gene in adult skeletal muscle in the absence of PPARα. However, among transcripts from other PPARα and PPARδ target genes, only those acutely induced by milk intake in wild-type neonates were altered in muscle or heart from PPARα-null neonates. Thus, PPARα-dependent regulation is required for appropriate gene regulation of UCP3 as part of the subset of fatty-acid-responsive genes in neonatal muscle and heart.

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