Tankyrase inhibition ameliorates lipid disorder via suppression of PGC-1α PARylation in db/db mice.

Objective: Human TNKS, encoding tankyrase 1 (TNKS1), localizes to a susceptibility locus for obesity and type 2 diabetes mellitus (T2DM). Here, we addressed the therapeutic potential of G007-LK, a TNKS-specific inhibitor, for obesity and T2DM.

Methods: We administered G007-LK to diabetic db/db mice and measured the impact on body weight, abdominal adiposity, and serum metabolites.

Adipose tissue mitochondrial capacity associates with long-term weight loss success.

Objectives: We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.

Methods: SAT biopsies were obtained from 19 clinically healthy obese subjects (body mass index (BMI) 34.6±2.

Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity.

The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health.

Weight Loss Is Associated With Increased NAD(+)/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue.

Context: Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) are 2 important nicotinamide adenine dinucleotide (NAD)(+)-dependent enzyme families with opposing metabolic effects. Energy shortage increases NAD(+) biosynthesis and SIRT activity but reduces PARP activity in animals. Effects of energy balance on these pathways in humans are unknown.

Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins.

Context: Sirtuins (SIRTs) regulate cellular metabolism and mitochondrial function according to the energy state of the cell reflected by NAD(+) levels.

Objective: Our aim was to determine whether expressions of SIRTs and NAD(+) biosynthesis genes are affected by acquired obesity and how possible alterations are connected with metabolic dysfunction while controlling for genetic and familial factors.

Design And Participants: We studied a cross-sectional sample of 40 healthy pairs of monozygotic twins, including 26 pairs who were discordant for body mass index (within-pair difference > 3 kg/m(2)), from the FinnTwin12 and FinnTwin16 cohorts.