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Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
The results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin–cAMP axis in liver. Expand
A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.
Findings show that in the context of a dietary pattern that includes high fat consumption, BCAA contributes to development of obesity-associated insulin resistance. Expand
Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance.
Target metabolomics finds that obesity-related insulin resistance in skeletal muscle is characterized by excessive beta-oxidation, impaired switching to carbohydrate substrate during the fasted-to-fed transition, and coincident depletion of organic acid intermediates of the tricarboxylic acid cycle. Expand
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
It is reported that the ketone body d-β-hydroxybutyrate (βOHB) is an endogenous and specific inhibitor of class I histone deacetylases (HDACs), and treatment of mice with βOHB conferred substantial protection against oxidative stress. Expand
Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion.
It is concluded that clonal selection of INS-1 cells allows isolation of cell lines that exhibit markedly enhanced and stable responsiveness to glucose and several of its known potentiators, which may be attractive new vehicles for studies of beta-cell function. Expand
SIRT 3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation
Sirtuins are NAD-dependent protein deacetylases. They mediate adaptive responses to a variety of stresses, including calorie restriction and metabolic stress. Sirtuin 3 (SIRT3) is localized in theExpand
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice
The results reveal that transmissible and modifiable interactions between diet and microbiota influence host biology and that adiposity is transmissible from human to mouse and that it was associated with changes in serum levels of branched-chain amino acids. Expand
Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes
This epidemiological reality heightens the urgency for gaining a deeper understanding of the processes that cause metabolic failure of key tissues and organ systems in type 2 diabetes, as reviewed here. Expand
Circadian Clock NAD+ Cycle Drives Mitochondrial Oxidative Metabolism in Mice
The results show that the circadian clock generates oscillations in mitochondrial oxidative capacity through rhythmic regulation of NAD+ biosynthesis, and facilitates oxidative rhythms that correspond with the fasting-feeding cycle to maximize energy production during rest. Expand
Hyperlipidemic Effects of Dietary Saturated Fats Mediated through PGC-1β Coactivation of SREBP
It is shown here that high-fat feeding, which induces hyperlipidemia and atherogenesis, stimulates the expression of both PGC-1beta and SREBP1c and 1a in liver, suggesting a mechanism through which dietary saturated fats can stimulate hyperlipIDemia and Atherogenesis. Expand