Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice

Abstract

Background

Kisspeptin is a neuropeptide that plays an integral role in the regulation of energy intake and reproduction by acting centrally on the hypothalamus–pituitary–gonadal axis. Our current study explores for the first time the effects of a pharmacological treatment of intraperitoneal kisspeptin-10 on murine feeding behavior, respirometry parameters, energy balance, and metabolic hormones.

Methods

Two groups (n = 16) of age- and sex-matched C57BL/6 wild-type adult mice were individually housed in metabolic cages and intraperitoneally injected with either kisspeptin-10 (2 nmol in 200 µl of saline) (10 µM) or vehicle before the beginning of a dark-phase cycle. Microstructure of feeding and drinking behavior, respirometry gases, respiratory quotient (RQ), total energy expenditure (TEE), metabolic hormones, oral glucose tolerance, and lipid profiles were measured.

Results

Intraperitoneal treatment with kisspeptin-10 caused a significant reduction in food intake, meal frequency, meal size, and eating rate. Kisspeptin-10 significantly decreased TEE during both the dark and light phase cycles, while also increasing the RQ during the dark-phase cycle. In addition, mice injected with kisspeptin-10 had significantly higher plasma levels of insulin (343.8 pg/ml vs. 106.4 pg/ml; p = 0.005), leptin (855.5 pg/ml vs. 173.1 pg/ml; p = 0.02), resistin (9411.1 pg/ml vs. 4116.5 pg/ml; p = 0.001), and HDL (147.6 mg/dl vs 97.1 mg/dl; p = 0.04).

Conclusion

A pharmacological dose of kisspeptin-10 significantly altered metabolism by suppressing food intake, meal size, eating rate, and TEE while increasing the RQ. These changes were linked to increased levels of insulin, leptin, resistin, and HDL. The current results suggest that a peripheral kisspeptin treatment could alter metabolism and energy homeostasis by suppressing appetite, food intake, and fat accumulation.

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Acknowledgments

Grant support NIH T32 DK 07180 (TD).

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Correspondence to Tien S. Dong.

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All animal research procedures were approved by the Department of Veterans Affair Institutional Animal Care and Use Committee (Protocol #03016-05).

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Dong, T.S., Vu, J.P., Oh, S. et al. Intraperitoneal Treatment of Kisspeptin Suppresses Appetite and Energy Expenditure and Alters Gastrointestinal Hormones in Mice. Dig Dis Sci 65, 2254–2263 (2020). https://doi.org/10.1007/s10620-019-05950-7

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Keywords

  • Kisspeptin-10
  • Metabolism
  • Insulin
  • Leptin
  • Resistin