Low-Carbohydrate, High-Protein Diet Affects Rhythmic Expression of Gluconeogenic Regulatory and Circadian Clock Genes in Mouse Peripheral Tissues

Jul 25, 2012Chronobiology international

Low-carb, high-protein diet changes daily patterns of blood sugar control and body clock genes in mouse tissues

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Abstract

A low-carbohydrate high-protein diet (HPD) significantly advanced the circadian clock in peripheral tissues of mice.

Mice on the HPD maintained normal circadian rhythms of locomotor activity and core body temperature, indicating no disruption of the central clock.
Feeding HPD for two weeks resulted in mild hypoglycemia while body weight remained unchanged, despite increased caloric intake compared to normal diet mice.
Plasma insulin levels in HPD mice were elevated during the inactive phase, contrasting with the pattern observed in normal diet mice.
Key gluconeogenic regulatory genes, PEPCK and G6Pase, were significantly upregulated in the liver and kidneys of HPD mice.
Activation of peroxisome proliferator-activated receptor α (PPARα) was suggested by increased mRNA levels of PPARα and its target genes in HPD mice.
Circadian mRNA expression of several clock genes was significantly phase-advanced in HPD mice, with elevated levels of BMAL1 and Cry1 in peripheral tissues.

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Recent studies have demonstrated that metabolic changes in mammals induce feedback regulation of the circadian clock. The present study evaluates the effects of a low-carbohydrate high-protein diet (HPD) on circadian behavior and peripheral circadian clocks in mice. Circadian rhythms of locomotor activity and core body temperature remained normal in mice fed with the HPD diet (HPD mice), suggesting that it did not affect the central clock in the hypothalamus. Two weeks of HPD feeding induced mild hypoglycemia without affecting body weight, although these mice consumed more calories than mice fed with a normal diet (ND mice). Plasma insulin levels were increased during the inactive phase in HPD mice, but increased twice, beginning and end of the active phase, in ND mice. Expression levels of the key gluconeogenic regulatory genes PEPCK and G6Pase were significantly induced in the liver and kidneys of HPD mice. The HPD appeared to induce peroxisome proliferator-activated receptor α (PPARα) activation, since mRNA expression levels of PPARα and its typical target genes, such as PDK4 and Cyp4A10, were significantly increased in the liver and kidneys. Circadian mRNA expression of clock genes, such as BMAL1, Cry1, NPAS2, and Rev-erbα, but not Per2, was significantly phase-advanced, and mean expression levels of BMAL1 and Cry1 mRNAs were significantly elevated, in the liver and kidneys of HPD mice. These findings suggest that a HPD not only affects glucose homeostasis, but that it also advances the molecular circadian clock in peripheral tissues.

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Low-Carbohydrate, High-Protein Diet Affects Rhythmic Expression of Gluconeogenic Regulatory and Circadian Clock Genes in Mouse Peripheral Tissues

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