Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 117, Issue 6, Pages 1658-1669Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI31561
Keywords
-
Categories
Funding
- NHLBI NIH HHS [P50 HL056989, HL56989] Funding Source: Medline
- NIDDK NIH HHS [DK73227, K01 DK060484, R01 DK033651, P30 DK063491, DK074868, DK60484, P01 DK074868, DK063491, R37 DK033651, DK33651, R21 DK073227] Funding Source: Medline
- NIGMS NIH HHS [GM069338, U54 GM069338] Funding Source: Medline
Ask authors/readers for more resources
PPAR gamma is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPAR gamma in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPAR gamma following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available