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Alterations in Oxygen Consumption, Respiratory Quotient, and Heat Production in Long-Lived GHRKO and


Jan 6, 2015


Growth hormone (GH) signaling influences longevity in mice, with decreased GH signaling associated with longer life span and increased GH signaling with shortened life span. A proposed mechanism through which GH signaling influences life span postulates that decreased GH signaling lowers metabolic rate, thus slowing aging by decreasing production of damaging free radicals. The influence of altered GH signaling on metabolism was tested by monitoring oxygen consumption (VO2), respiratory quotient (RQ), and heat production in long-lived GH receptor knockout (GHRKO) and Ames dwarf mice, and short-lived bovine GH-overexpressing transgenic (bGH TG) mice. Intriguingly, both GHRKO and Ames dwarf mice have increased VO2 and heat per gram body weight, and decreased RQ, whereas bGH TG mice have decreased VO2 and heat per gram body weight and increased RQ. In conclusion, decreased GH signaling associates with increased metabolism per body weight and may beneficially affect mitochondrial flexibility by increasing the capacity for fat oxidation; generally, GH excess produces opposite metabolic effects.

In summary, this study shows that both long-lived Ames dwarf and GHRKO mice have increased VO2 and heat expressed per gram, and decreased RQ compared with normal controls, whereas short-lived bGH TG mice have reduced VO2 and heat expressed per gram body weight, and increased RQ compared with their corresponding controls. In addition, we have shown that male GHRKO mice have increased T3 levels and T3/T4 ratio, whereas male bGH TG mice have no significant change in thyroid hormone levels compared with normal controls. These data show that alterations in GH signaling cause marked changes in energy metabolism. Decreased GH signaling causes increased T3 (GHRKO), increased metabolism per body weight, increased fatty acid oxidation, and may have a beneficial effect on mitochondrial flexibility by increasing the ability to utilize fat as a fuel substrate, whereas GH excess has generally opposite effects in mice. These results indicate that increased metabolism is associated with increased life span in these mice.

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