Neurosecretory protein GL stimulates food intake, de novo lipogenesis, and onset of obesity
Eiko Iwakoshi-Ukena,
Kenshiro Shikano,
Kunihiro Kondo,
Shusuke Taniuchi,
Megumi Furumitsu,
Yuta Ochi,
Tsutomu Sasaki,
Shiki Okamoto,
George E Bentley,
Lance J Kriegsfeld,
Yasuhiko Minokoshi,
Kazuyoshi Ukena
Affiliations
Eiko Iwakoshi-Ukena
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan; Department of Integrative Biology and The Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, United States
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan
Kunihiro Kondo
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan
Shusuke Taniuchi
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan
Megumi Furumitsu
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan
Yuta Ochi
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan
Tsutomu Sasaki
Laboratory of Metabolic Signal, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
Shiki Okamoto
Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, Sokendai (The Graduate University for Advanced Studies), Hayama, Japan; Second Department of Internal Medicine (Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology), Graduate School of Medicine, University of the Ryukyus, Nakagami-gun, Japan
George E Bentley
Department of Integrative Biology and The Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, United States
Lance J Kriegsfeld
Department of Psychology and The Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, United States
Yasuhiko Minokoshi
Division of Endocrinology and Metabolism, Department of Homeostatic Regulation, National Institute for Physiological Sciences, Okazaki, Japan; Department of Physiological Sciences, School of Life Science, Sokendai (The Graduate University for Advanced Studies), Hayama, Japan
Section of Behavioral Sciences, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi-Hiroshima, Japan; Department of Psychology and The Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, United States
Mechanisms underlying the central regulation of food intake and fat accumulation are not fully understood. We found that neurosecretory protein GL (NPGL), a newly-identified neuropeptide, increased food intake and white adipose tissue (WAT) in rats. NPGL-precursor gene overexpression in the hypothalamus caused increases in food intake, WAT, body mass, and circulating insulin when fed a high calorie diet. Intracerebroventricular administration of NPGL induced de novo lipogenesis in WAT, increased insulin, and it selectively induced carbohydrate intake. Neutralizing antibody administration decreased the size of lipid droplets in WAT. Npgl mRNA expression was upregulated by fasting and low insulin levels. Additionally, NPGL-producing cells were responsive to insulin. These results point to NPGL as a novel neuronal regulator that drives food intake and fat deposition through de novo lipogenesis and acts to maintain steady-state fat level in concert with insulin. Dysregulation of NPGL may be a root cause of obesity.
