G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice

Olivia Osborn, Dayoung Oh, Joanne McNelis, Manuel Sanchez-Alavez, Saswata Talukdar, Min Lu, Ping Ping Li, Lucinda Thiede, Hidetaka Morinaga, Jane J. Kim, Jan Heinrichsdorff, Sarah Nalbandian, Jachelle M. Ofrecio, Miriam Scadeng, Simon Schenk, John Hadcock, Tamas Bartfai, Jerrold M. Olefsky

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Obesity-induced inflammation is a key component of systemic insulin resistance, which is a hallmark of type 2 diabetes. A major driver of this inflammation/insulin resistance syndrome is the accumulation of proinflammatory macrophages in adipose tissue and liver. We found that the orphan GPCR Gpr21 was highly expressed in the hypothalamus and macrophages of mice and that whole-body KO of this receptor led to a robust improvement in glucose tolerance and systemic insulin sensitivity and a modest lean phenotype. The improvement in insulin sensitivity in the high-fat diet-fed (HFD-fed) Gpr21 KO mouse was traced to a marked reduction in tissue inflammation caused by decreased chemotaxis of Gpr21 KO macrophages into adipose tissue and liver. Furthermore, mice lacking macrophage expression of Gpr21 were protected from HFD-induced inflammation and displayed improved insulin sensitivity. Results of in vitro chemotaxis studies in human monocytes suggested that the defect in chemotaxis observed ex vivo and in vivo in mice is also translatable to humans. Cumulatively, our data indicate that GPR21 has a critical function in coordinating macrophage proinflammatory activity in the context of obesity-induced insulin resistance.

Original languageEnglish (US)
Pages (from-to)2444-2453
Number of pages10
JournalJournal of Clinical Investigation
Volume122
Issue number7
DOIs
StatePublished - Jul 2 2012

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Obese Mice
G-Protein-Coupled Receptors
Insulin Resistance
Diet
Macrophages
Chemotaxis
Inflammation
Adipose Tissue
Obesity
Orphaned Children
Liver
High Fat Diet
Type 2 Diabetes Mellitus
Hypothalamus
Monocytes
Phenotype
Glucose

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Osborn, O., Oh, D., McNelis, J., Sanchez-Alavez, M., Talukdar, S., Lu, M., ... Olefsky, J. M. (2012). G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. Journal of Clinical Investigation, 122(7), 2444-2453. https://doi.org/10.1172/JCI61953

G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. / Osborn, Olivia; Oh, Dayoung; McNelis, Joanne; Sanchez-Alavez, Manuel; Talukdar, Saswata; Lu, Min; Li, Ping Ping; Thiede, Lucinda; Morinaga, Hidetaka; Kim, Jane J.; Heinrichsdorff, Jan; Nalbandian, Sarah; Ofrecio, Jachelle M.; Scadeng, Miriam; Schenk, Simon; Hadcock, John; Bartfai, Tamas; Olefsky, Jerrold M.

In: Journal of Clinical Investigation, Vol. 122, No. 7, 02.07.2012, p. 2444-2453.

Research output: Contribution to journalArticle

Osborn, O, Oh, D, McNelis, J, Sanchez-Alavez, M, Talukdar, S, Lu, M, Li, PP, Thiede, L, Morinaga, H, Kim, JJ, Heinrichsdorff, J, Nalbandian, S, Ofrecio, JM, Scadeng, M, Schenk, S, Hadcock, J, Bartfai, T & Olefsky, JM 2012, 'G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice', Journal of Clinical Investigation, vol. 122, no. 7, pp. 2444-2453. https://doi.org/10.1172/JCI61953
Osborn, Olivia ; Oh, Dayoung ; McNelis, Joanne ; Sanchez-Alavez, Manuel ; Talukdar, Saswata ; Lu, Min ; Li, Ping Ping ; Thiede, Lucinda ; Morinaga, Hidetaka ; Kim, Jane J. ; Heinrichsdorff, Jan ; Nalbandian, Sarah ; Ofrecio, Jachelle M. ; Scadeng, Miriam ; Schenk, Simon ; Hadcock, John ; Bartfai, Tamas ; Olefsky, Jerrold M. / G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. In: Journal of Clinical Investigation. 2012 ; Vol. 122, No. 7. pp. 2444-2453.
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