Aryl hydrocarbon receptor AHR agonists such as dioxin have been associated with obesity and the development of diabetes. Whole-body Ahr knockout mice on high-fat diet HFD have been shown to resist obesity and hepatic steatosis. Tissue-specific knockout of Ahr in mature adipocytes via adiponectin-Cre exacerbates obesity while knockout in liver increases steatosis without having significant effects on obesity. Our previous studies demonstrated that treatment of subcutaneous preadipocytes with exogenous or endogenous AHR agonists disrupts maturation into functional adipocytes in vitro. On a regular control diet, knockout and non-knockout mice showed no differences in weight gain, indicating the protective phenotype arises only when animals are challenged by a HFD. Metabolic syndrome, a cluster of conditions i. Adipose tissue is critical for normal metabolism and its dysfunction plays an essential role in the development of metabolic syndrome [ 4 — 6 ]. Adipose tissue is necessary for regulation of inflammation as well as secretion of adipokines such as adiponectin and leptin [ 7 ]. Adipose tissue is much more diverse than previously appreciated and brown, white, and beige adipose tissues play distinct roles in energy homeostasis.
However, the increase of lipogenesis activity was attenuated by the overexpression of SOCS3 in the liver Fig. Right panel, the colony number of inflammatory cells per high power field. Metabolic syndrome, a cluster of conditions i. Consider the following examples, but note that this is not an exhaustive list: Examples of ‘Non-Financial Competing Interests’ Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. Glucose and insulin tolerance tests Following a 6-hour fast, time 0 blood was collected via tail bleed followed by an intraperitoneal i. Neither of the above. Tail blood was collected and plasma glucose analyzed as described above. While the identity of this metabolite is unknown, there is evidence that HFD can alter levels of known AHR agonists such as tryptophan catabolites generated in the kynurenine pathway, for example [ 68 ].
Aryl hydrocarbon receptor AhR is a ligand-activated transcription factor regulating the expression of genes involved in xenobiotic response. Recent studies have suggested that AhR plays essential roles not only in xenobiotic detoxification but also energy metabolism. Thus, in this study, we studied the roles of AhR in lipid metabolism. Gene expression analysis and biochemical study revealed that de novo lipogenesis activity was significantly increased in AhR LKO mice. Promoter analysis established Socs3 as novel transcriptional target of AhR. These results indicated that AhR plays a protective role against HFD-induced hepatic steatosis and the subsequent lipotoxicity effects, such as inflammation, and that the mechanism of protection involves the direct transcriptional regulation of Socs3 expression by AhR. Upon binding to ligands, AhR forms a heterodimer with the AhR nuclear translocator Arnt in the nucleus.