Involvement of progranulin in hypothalamic glucose sensing and feeding regulation

Hyun Kyong Kim, Mi Seon Shin, Byung Soo Youn, Churl Namkoong, So Young Gil, Gil Myoung Kang, Ji Hee Yu, Min Seon Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions, including modulation of wound healing and inflammation. Hypothalamic PGRN has been implicated in the development of sexual dimorphism. In the present study, a potential role for PGRN in the hypothalamic regulation of appetite and body weight was investigated. In adult rodents, PGRN was highly expressed in periventricular tanycytes and in hypothalamic neurons, which are known to contain glucose-sensing machinery. Hypothalamic PGRN expression levels were decreased under low-energy conditions (starvation and 2-deoxy-D-glucose administration) but increased under high-energy condition (postprandially). Intracerebrovetricular administration of PGRN significantly suppressed nocturnal feeding as well as hyperphagia induced by 2-deoxyglucose, neuropeptide Y, and Agouti-related peptide. Moreover, the inhibition of hypothalamic PGRN expression or action increased food intake and promoted weight gain, suggesting that endogenous PGRN functions as an appetite suppressor in the hypothalamus. Investigation of the mechanism of action revealed that PGRN diminished orexigenic neuropeptide Y and Agouti-related peptide production but stimulated anorexigenic proopiomelanocortin production, at least in part through the regulation of hypothalamic AMP-activated protein kinase. Notably, PGRN was also expressed in hypothalamic microglia. In diet-induced obese mice, microglial PGRN expression was increased, and the anorectic response to PGRN was blunted. These findings highlight a physiological role for PGRN in hypothalamic glucose-sensing and appetite regulation. Alterations in hypothalamic PGRN production or action may be linked to appetite dysregulation in obesity.

Original languageEnglish
Pages (from-to)4672-4682
Number of pages11
JournalEndocrinology
Volume152
Issue number12
DOIs
Publication statusPublished - 2011 Dec 1
Externally publishedYes

Fingerprint

Appetite Regulation
Neuropeptide Y
Deoxyglucose
Appetite
Ependymoglial Cells
Glucose
Appetite Depressants
Obese Mice
Pro-Opiomelanocortin
Hyperphagia
Peptides
AMP-Activated Protein Kinases
Microglia
Starvation
Sex Characteristics
Wound Healing
Hypothalamus
Weight Gain
Rodentia
Glycoproteins

ASJC Scopus subject areas

  • Endocrinology

Cite this

Kim, H. K., Shin, M. S., Youn, B. S., Namkoong, C., Gil, S. Y., Kang, G. M., ... Kim, M. S. (2011). Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. Endocrinology, 152(12), 4672-4682. https://doi.org/10.1210/en.2011-1221

Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. / Kim, Hyun Kyong; Shin, Mi Seon; Youn, Byung Soo; Namkoong, Churl; Gil, So Young; Kang, Gil Myoung; Yu, Ji Hee; Kim, Min Seon.

In: Endocrinology, Vol. 152, No. 12, 01.12.2011, p. 4672-4682.

Research output: Contribution to journalArticle

Kim, HK, Shin, MS, Youn, BS, Namkoong, C, Gil, SY, Kang, GM, Yu, JH & Kim, MS 2011, 'Involvement of progranulin in hypothalamic glucose sensing and feeding regulation', Endocrinology, vol. 152, no. 12, pp. 4672-4682. https://doi.org/10.1210/en.2011-1221
Kim HK, Shin MS, Youn BS, Namkoong C, Gil SY, Kang GM et al. Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. Endocrinology. 2011 Dec 1;152(12):4672-4682. https://doi.org/10.1210/en.2011-1221
Kim, Hyun Kyong ; Shin, Mi Seon ; Youn, Byung Soo ; Namkoong, Churl ; Gil, So Young ; Kang, Gil Myoung ; Yu, Ji Hee ; Kim, Min Seon. / Involvement of progranulin in hypothalamic glucose sensing and feeding regulation. In: Endocrinology. 2011 ; Vol. 152, No. 12. pp. 4672-4682.
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