Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice
It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated therm...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Zietak, M., Kozak, L. P. Tags: Articles Source Type: research
CTRP3 deficiency reduces liver size and alters IL-6 and TGF{beta} levels in obese mice
C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD)...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Wolf, R. M., Lei, X., Yang, Z.-C., Nyandjo, M., Tan, S. Y., Wong, G. W. Tags: Articles Source Type: research
Modeling changes in glucose and glycerol rates of appearance when true basal rates of appearance cannot be readily determined
Advancing diabetes care requires accurate physiological assessments. Hyperinsulinemic clamps with stable isotope tracers can simultaneously measure insulin's ability to suppress lipolysis and hepatic glucose release. Traditionally, these methods require an assessment of basal glucose and glycerol rate of appearance (Ra). Basal Ra is challenging to measure in insulin-dependent diabetes, where exogenous insulin required to maintain normoglycemia can raise peripheral insulin concentrations sufficiently to suppress basal Ra. Thus we identified two alternative statistical approaches to describe changes in glucose and glycerol R...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Pyle, L., Bergman, B. C., Nadeau, K. J., Cree-Green, M. Tags: Innovative Methodology Source Type: research
2-Methoxyestradiol, an endogenous 17{beta}-estradiol metabolite, inhibits microglial proliferation and activation via an estrogen receptor-independent mechanism
17β-Estradiol (estradiol) inhibits microglia proliferation. 2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with little affinity for estrogen receptors (ERs). We hypothesize that 2-ME inhibits microglial proliferation and activation and contributes to estradiol's inhibitory effects on microglia. We compared the effects of estradiol, 2-hydroxyestradiol [2-OE; estradiol metabolite produced by cytochrome P450 (CYP450)], and 2-ME [formed by catechol-O-methyltransferase (COMT) acting upon 2-OE] on microglial (BV2 cells) DNA synthesis, cell proliferation, activation, and phagocytosis. 2-ME and 2-OE were a...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Schaufelberger, S. A., Rosselli, M., Barchiesi, F., Gillespie, D. G., Jackson, E. K., Dubey, R. K. Tags: Call for Papers Source Type: research
Profound hyperglycemia in knockout mutant mice identifies novel function for POU4F2/Brn-3b in regulating metabolic processes
The POU4F2/Brn-3b transcription factor has been identified as a potentially novel regulator of key metabolic processes. Loss of this protein in Brn-3b knockout (KO) mice causes profound hyperglycemia and insulin resistance (IR), normally associated with type 2 diabetes (T2D), whereas Brn-3b is reduced in tissues taken from obese mice fed on high-fat diets (HFD), which also develop hyperglycemia and IR. Furthermore, studies in C2C12 myocytes show that Brn-3b mRNA and proteins are induced by glucose but inhibited by insulin, suggesting that this protein is itself highly regulated in responsive cells. Analysis of differential...
Source: AJP: Endocrinology and Metabolism - March 1, 2016 Category: Endocrinology Authors: Bitsi, S., Ali, H., Maskell, L., Ounzain, S., Mohamed-Ali, V., Budhram-Mahadeo, V. S. Tags: Call for Papers Source Type: research
