Importance of Adipose Tissue NAD+ Biology in Regulating Metabolic Flexibility.

Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme that regulates cellular energy metabolism in many cell types. The major purpose of the present study was to test the hypothesis that NAD+ in white adipose tissue (WAT) is a regulator of whole-body metabolic flexibility in response to changes in insulin sensitivity and with respect to substrate availability and use during feeding and fasting conditions. To this end, we first evaluated the relationship between WAT NAD+ concentration and metabolic flexibility in mice and humans.

Adipose tissue NAD biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice.

Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase () knockout (ANKO) and brown adipocyte-specific knockout (BANKO) mice because NAMPT is the rate-limiting NAD biosynthetic enzyme.

Diurnal Variation in PDK4 Expression Is Associated With Plasma Free Fatty Acid Availability in People.

Context: Many biological pathways involved in regulating substrate metabolism display rhythmic oscillation patterns. In rodents, clock genes regulate circadian rhythms of metabolic genes and substrate metabolism. However, the interrelationships among substrate metabolism, metabolic genes, and clock genes have not been fully explored in people.

NAMPT-Mediated NAD(+) Biosynthesis in Adipocytes Regulates Adipose Tissue Function and Multi-organ Insulin Sensitivity in Mice.

Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people.

Protein Ingestion Induces Muscle Insulin Resistance Independent of Leucine-Mediated mTOR Activation.

Increased plasma branched-chain amino acid concentrations are associated with insulin resistance, and intravenous amino acid infusion blunts insulin-mediated glucose disposal. We tested the hypothesis that protein ingestion impairs insulin-mediated glucose disposal by leucine-mediated mTOR signaling, which can inhibit AKT. We measured glucose disposal and muscle p-mTOR(Ser2448), p-AKT(Ser473), and p-AKT(Thr308) in 22 women during a hyperinsulinemic-euglycemic clamp procedure with and without concomitant ingestion of whey protein (0.

Sterculic Oil, a Natural SCD1 Inhibitor, Improves Glucose Tolerance in Obese ob/ob Mice.

Obesity and its metabolic complications are associated with increased expression/activity of stearoyl-CoA desaturase-1 (SCD1), a major regulator of lipid metabolism. Reduction or ablation of this enzyme is associated with an improved metabolic profile and has gained attention as a target for pharmaceutical development. Sterculic oil (SO) is a known inhibitor of SCD1 and may provide a natural approach for treating obesity and/or insulin resistance.

A comparison of inflammatory and oxidative stress markers in adipose tissue from weight-matched obese male and female mice.

Expansion of intra-abdominal adipose tissue and the accompanying inflammatory response has been put forward as a unifying link between obesity and the development of chronic diseases. However, an apparent sexual dimorphism exists between obesity and chronic disease risk due to differences in the distribution and abundance of adipose tissue. A range of experimental protocols have been employed to demonstrate the role of estrogen in regulating health benefits; however, most studies are confounded by significant differences in body weight and adiposity.