Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight

Hyun Kyong Kim, Byung Soo Youn, Mi Seon Shin, Churl Namkoong, Kyeong Han Park, Ja-Hyun Baik, Jae Bum Kim, Joong Yeol Park, Ki Up Lee, Young Bum Kim, Min Seon Kim

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

OBJECTIVE - The angiopoietin-like protein 4 (Angptl4)/fasting-induced adipose factor (Fiaf) is known as a regulator of peripheral lipid and glucose metabolism. In the present study, we investigated the physiological role of Angptl4 in central regulation of body weight homeostasis. RESEARCH DESIGN AND METHODS - Hypothalamic Angptl4 expression levels were measured using immunoblot assay during feeding manipulation or after administration of leptin, insulin, and nutrients. The effects of Angptl4 on food intake, body weight, and energy expenditure were determined following intracerebroventricular (ICV) administration of Angptl4 in C57BL/6 mice. Food intake, energy metabolism, and feeding responses to leptin, insulin, and nutrients were compared between Angptl4-null mice and their wild littermates. Finally, the relationship of hypothalamic AMP-activated protein kinase (AMPK) and Angptl4 was studied. RESULTS - Hypothalamic Angptl4 expression levels were increased upon food intake or administration of leptin, insulin, and nutrients. Furthermore, central administration of Angptl4 suppressed food intake and body weight gain but enhanced energy expenditure. These effects were mediated via suppression of hypothalamic AMPK activities. Consistently, Angptl4-null mice displayed increased body weight and hypothalamic AMPK activity but reduced energy expenditure. Food intake following a fast was significantly greater in Angptl4-null mice, which was normalized by centrally administered Angptl4. Moreover, anorectic responses to leptin, insulin, and glucose were diminished in Angptl4-null mice. In contrast, Angptl4-null mice were resistant to diet-induced obesity, indicating obesity-promoting effects of Angptl4 under the condition of fat-enriched diet. CONCLUSIONS - We have demonstrated that hypothalamic Angptl4 is regulated by physiological appetite regulators and mediates their anorexigenic effects via inhibition of hypothalamic AMPK activity. Therefore, Angptl4 appears to have an important role in central regulation of energy metabolism.

Original languageEnglish
Pages (from-to)2772-2780
Number of pages9
JournalDiabetes
Volume59
Issue number11
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Angiopoietins
Fasting
Eating
Body Weight
Proteins
AMP-Activated Protein Kinases
Energy Metabolism
Leptin
Insulin
Food
Obesity
Diet
Glucose
Appetite Depressants
Appetite
Inbred C57BL Mouse
Lipid Metabolism
Weight Gain

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kim, H. K., Youn, B. S., Shin, M. S., Namkoong, C., Park, K. H., Baik, J-H., ... Kim, M. S. (2010). Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. Diabetes, 59(11), 2772-2780. https://doi.org/10.2337/db10-0145

Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. / Kim, Hyun Kyong; Youn, Byung Soo; Shin, Mi Seon; Namkoong, Churl; Park, Kyeong Han; Baik, Ja-Hyun; Kim, Jae Bum; Park, Joong Yeol; Lee, Ki Up; Kim, Young Bum; Kim, Min Seon.

In: Diabetes, Vol. 59, No. 11, 01.11.2010, p. 2772-2780.

Research output: Contribution to journalArticle

Kim, HK, Youn, BS, Shin, MS, Namkoong, C, Park, KH, Baik, J-H, Kim, JB, Park, JY, Lee, KU, Kim, YB & Kim, MS 2010, 'Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight', Diabetes, vol. 59, no. 11, pp. 2772-2780. https://doi.org/10.2337/db10-0145
Kim HK, Youn BS, Shin MS, Namkoong C, Park KH, Baik J-H et al. Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. Diabetes. 2010 Nov 1;59(11):2772-2780. https://doi.org/10.2337/db10-0145
Kim, Hyun Kyong ; Youn, Byung Soo ; Shin, Mi Seon ; Namkoong, Churl ; Park, Kyeong Han ; Baik, Ja-Hyun ; Kim, Jae Bum ; Park, Joong Yeol ; Lee, Ki Up ; Kim, Young Bum ; Kim, Min Seon. / Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. In: Diabetes. 2010 ; Vol. 59, No. 11. pp. 2772-2780.
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AU - Park, Kyeong Han

AU - Baik, Ja-Hyun

AU - Kim, Jae Bum

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AU - Kim, Young Bum

AU - Kim, Min Seon

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