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Diabetes, Vol 48, Issue 9 1822-1829, Copyright © 1999 by American Diabetes Association
Increased glucose metabolism and insulin sensitivity in transgenic skinny mice overexpressing leptin
Y Ogawa, H Masuzaki, K Hosoda, M Aizawa-Abe, J Suga, M Suda, K Ebihara, H Iwai, N Matsuoka, N Satoh, H Odaka, H Kasuga, Y Fujisawa, G Inoue, H Nishimura, Y Yoshimasa and K Nakao
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan. ogawa@kuhp.kyoto-u.ac.jp
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.

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Copyright © 1999 by the American Diabetes Association.
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