Fibroblast activation protein is dispensable for control of glucose homeostasis and body weight in mice.

Objective: Fibroblast Activation Protein (FAP), an enzyme structurally related to dipeptidyl peptidase-4 (DPP-4), has garnered interest as a potential metabolic drug target due to its ability to cleave and inactivate FGF-21 as well as other peptide substrates. Here we investigated the metabolic importance of FAP for control of body weight and glucose homeostasis in regular chow-fed and high fat diet-fed mice.

Methods: FAP enzyme activity was transiently attenuated using a highly-specific inhibitor CPD60 and permanently ablated by genetic inactivation of the mouse Fap gene.

Human FGF-21 Is a Substrate of Fibroblast Activation Protein.

FGF-21 is a key regulator of metabolism and potential drug candidate for the treatment of type II diabetes and other metabolic disorders. However, the half-life of active, circulating, human FGF-21 has recently been shown to be limited in mice and monkeys by a proteolytic cleavage between P171 and S172. Here, we show that fibroblast activation protein is the enzyme responsible for this proteolysis by demonstrating that purified FAP cleaves human FGF-21 at this site in vitro, and that an FAP-specific inhibitor, ARI-3099, blocks the activity in mouse, monkey and human plasma and prolongs the half-life of circulating human FGF-21 in mice.

The high-fat high-fructose hamster as an animal model for niacin's biological activities in humans.

Objective: Niacin has been used for more than 50 years to treat dyslipidemia, yet the mechanisms underlying its lipid-modifying effects remain unknown, a situation stemming at least in part from a lack of validated animal models. The objective of this study was to determine if the dyslipidemic hamster could serve as such a model.

Materials/methods: Dyslipidemia was induced in Golden Syrian hamsters by feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet.

The cellular YY1 transcription factor binds a cis-acting, negatively regulating element in the Epstein-Barr virus BRLF1 promoter.

Disruption of Epstein-Barr virus latency is induced by expression of either the BZLF1 (in B cells and epithelial cells) or BRLF1 (in epithelial cells only) immediate-early protein. Regulation of BZLF1 and BRLF1 transcription may therefore modulate the stringency of viral latency. The cellular transcription factor YY1 negatively regulates BZLF1 transcription.

Changes in thyroid function in pregnancy and with oral contraceptive use.

We measured T4, T3, T3 uptake, and TSH in nonpregnant patients, pregnant patients in the early and late first, and third trimesters, and patients using oral contraceptives. Mean T4 levels increased and T3 uptake decreased during pregnancy. Concentrations of T3 decreased in early pregnancy, then increased during the rest of pregnancy.