Abstract
Leptin signaling in the hypothalamus is crucial in energy homeostasis. We have previously shown that dietary deprivation of the essential amino acid leucine in mice stimulates fat loss by increasing energy expenditure. The involvement of leptin signaling in this regulation, however, has not been reported. Here, we show that leucine deprivation promotes leptin signaling in mice maintained on an otherwise normal diet and restores leptin responses in mice maintained on a high fat diet, a regimen known to induce leptin resistance. In addition, we found that leucine deprivation stimulated energy expenditure, and fat loss was largely blocked in db/db mice homozygous for a mutation in leptin receptor and a knock-in mouse line Y3F with abrogation of leptin receptor Tyr(1138)-mediated signal transducer and activator transcript 3 signaling. Overall, our studies describe a novel link between hypothalamic leptin signaling and stimulation of energy expenditure under leucine deprivation.
Highlights
Leucine deprivation decreases fat mass via enhancing energy expenditure; the involvement of leptin signaling is unknown
We show that leptin signaling is directly involved in the regulation of energy expenditure and fat loss during leucine deprivation, and the present evidence suggests that the signal
Leucine Deprivation Increases Leptin Signaling in Mice—To investigate the effects of leucine deprivation on leptin signaling, C57BL/6J wild-type (WT) mice were maintained on a leucinedeficient diet or control diet for 7 days, as described in our previous studies [24, 30, 31]
Summary
Leucine deprivation decreases fat mass via enhancing energy expenditure; the involvement of leptin signaling is unknown. Results: Leucine deprivation promoted leptin signaling, and the increased energy expenditure was blocked in leptin signalingdisrupted mice. Conclusion: Leptin signaling is required for leucine deprivation-increased energy expenditure. Significance: Our studies reveal a physiological mechanism linking leptin signaling with leucine deprivation-enhanced energy expenditure. We have previously shown that dietary deprivation of the essential amino acid leucine in mice stimulates fat loss by increasing energy expenditure. We found that leucine deprivation stimulated energy expenditure, and fat loss was largely blocked in db/db mice homozygous for a mutation in leptin receptor and a knock-in mouse line Y3F with abrogation of leptin receptor Tyr1138-mediated signal transducer and activator transcript 3 signaling. Our studies describe a novel link between hypothalamic leptin signaling and stimulation of energy expenditure under leucine deprivation
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