Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin

Yoshihiro Ogawa, Hiroaki Masuzaki, Kiminori Hosoda, Megumi Aizawa-Abe, Junko Suga, Michio Suda, Ken Ebihara, Hidenori Iwai, Naoki Matsuoka, Noriko Satoh, Hiroyuki Odaka, Hisao Kasuga, Yukio Fujisawa, Gen Inoue, Haruo Nishimura, Yasunao Yoshimasa, Kazuwa Nakao

Research output: Contribution to journalArticle

170 Citations (Scopus)

Abstract

Excess of body fat, or obesity, is a major health problem and confers a higher risk of cardiovascular and metabolic disorders such as diabetes, hypertension, and coronary heart disease. Leptin is an adipocyte-derived satiety factor that plays an important role in the regulation of energy homeostasis, and its synthesis and secretion are markedly increased in obese subjects. To explore the metabolic consequences of an increased amount of leptin on a long-term basis in vivo, we generated transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. Overexpression of leptin in the liver has resulted in complete disappearance of white and brown adipose tissue for a long period of time in mice. Transgenic skinny mice exhibit increased glucose metabolism accompanied by the activation of insulin signaling in the skeletal muscle and liver. They also show small-sized livers with a marked decrease in glycogen and lipid storage. The phenotypes are in striking contrast to those of recently reported animal models of lipoatrophic diabetes and patients with lipoatrophic diabetes with reduced amount of leptin. The present study provides evidence that leptin is an adipocyte-derived antidiabetic hormone in vivo and suggests its pathophysiologic and therapeutic implications in diabetes.

Original languageEnglish
Pages (from-to)1822-1829
Number of pages8
JournalDiabetes
Volume48
Issue number9
DOIs
Publication statusPublished - Sep 11 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Ogawa, Y., Masuzaki, H., Hosoda, K., Aizawa-Abe, M., Suga, J., Suda, M., Ebihara, K., Iwai, H., Matsuoka, N., Satoh, N., Odaka, H., Kasuga, H., Fujisawa, Y., Inoue, G., Nishimura, H., Yoshimasa, Y., & Nakao, K. (1999). Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin. Diabetes, 48(9), 1822-1829. https://doi.org/10.2337/diabetes.48.9.1822