Human CRP overexpression facilitated the development of insulin resistance and hepatosteatosis with HFD in association with adiponectin down-regulation and enhancement of macrophage infiltration and expression of pro-inflammatory cytokines in epididymal adipose tissue, suggesting its pathogenic role in the development of obesity-induced metabolic disorders.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has already been considered as an attractive molecular target for the treatment of human metabolic disorders.
Expression of the peroxisome proliferator activated receptor gamma gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes.
In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.
In the larger subset of T2DM, GHR(d3) was associated with higher CRP levels as well as age adjusted IGF-I, with a trend of higher C-peptide secretion and impaired lipid levels, indicating a phenotype with metabolic disorder when compared to the GHR(fl/fl) T2DM subjects.
In conclusion, the PPARGPro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life.
C333H has dual action on both PPARalpha and PPARgamma, and might be of interest for the amelioration of lipid metabolic disorders and insulin resistance associated with type 2 diabetes.
Paraoxonase 1 (PON1) is an important antiatherogenic and antioxidant enzyme in the circulation that has been associated with adverse health outcomes particularly cardiovascular disease (CVD) and other metabolic disorders.
L55M polymorphism, like exposure to tobacco smoke and overweight, disorders PON1 status and lipid profile parameters; therefore, it could be a crucial risk factor for the development of many metabolic disorders.
These results indicate that PON-1 is paradoxically maintained and may even be increased in NAFLD despite inverse associations with metabolic disorders and low HDL cholesterol.
SR-BI deficiency leading to dysfunctional HDL is closely related to alteration of HDL protein, suggesting that identification of apoAI, PON1, SAA, apoAIV, and A1AT may serve as the valuable protein markers for diagnosis and therapeutics of dysfunctional HDL-related metabolic diseases.
Interaction between prenatal pesticide exposure and a common polymorphism in the PON1 gene on DNA methylation in genes associated with cardio-metabolic disease risk-an exploratory study.
None of the variants of the Leu55MetPON1 polymorphism was associated with more frequent occurrence of PCOS or metabolic disorders, including insulin resistance.
These observations emphasize a role for AHR in the systemic homeostatic regulation of cholesterol synthesis and absorption, indicating the potential use of this receptor as a target for the treatment of hyperlipidosis-associated metabolic diseases.
Our findings establish a critical role of AhR in regulating PPARγ stability and suggest that the AhR-PPARγ interaction may represent a potential therapeutic target for managing metabolic diseases arising from PPARγ dysfunction.
The data demonstrate an important AHR-FGF21 regulatory axis that influences adipose biology and may represent a "druggable" therapeutic target for obesity and its related metabolic disorders.
Interestingly, many detoxification enzymes, including cytochrome P450s and flavin-containing monooxygenases, and their associated transcriptional activators [e.g. the aryl hydrocarbon receptor (AhR)], have now been shown to have endogenous roles in normal physiology and the pathology of metabolic diseases.
Further, dietary TCDF inhibited the farnesoid X receptor (FXR) signaling pathway, triggered significant inflammation and host metabolic disorders as a result of activation of bacterial fermentation, and altered hepatic lipogenesis, gluconeogenesis, and glycogenolysis in an AHR-dependent manner.