TitleDecreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans.
Publication TypeJournal Article
Year of Publication2011
AuthorsGauthier, M-S, O'Brien, EL, Bigornia, S, Mott, M, Cacicedo, JM, X Xu, J, Gokce, N, Apovian, C, Ruderman, N
JournalBiochem Biophys Res Commun
Date Published2011 Jan 07
KeywordsAdult, AMP-Activated Protein Kinases, Biomarkers, Body Mass Index, Female, Humans, Inflammation, Insulin Resistance, Intra-Abdominal Fat, Male, Middle Aged, Obesity

Inflammation and infiltration of immune cells in white adipose tissue have been implicated in the development of obesity-associated insulin resistance. Likewise, dysregulation of the fuel-sensing enzyme AMP-activated protein kinase (AMPK) has been proposed as a pathogenetic factor for these abnormalities based on both its links to insulin action and its anti-inflammatory effects. In this study, we examined the relationships between AMPK activity, the expression of multiple inflammatory markers in visceral (mesenteric and omental) and abdominal subcutaneous adipose tissue, and whole-body insulin sensitivity in morbidly obese patients (BMI 48±1.9 kg/m(2)) undergoing gastric bypass surgery. AMPK activity was assessed by Western-blots (P-AMPK/T-AMPK) and mRNA levels of various markers of inflammation by qRT-PCR. Patients were stratified as insulin sensitive obese or insulin-resistant obese according to their HOMA-IR values. The results indicate that AMPK activity is lower in visceral than in subcutaneous abdominal adipose tissue of these patients and that this is associated with an increased expression of multiple inflammatory genes. They also revealed that AMPK activity is lower in adipose tissue of obese patients who are insulin resistant (HOMA-IR>2.3) than in BMI-matched insulin sensitive subjects. Furthermore, this difference was evident in all three fat depots. In conclusion, the data suggest that there are close links between reduced AMPK activity and inflammation in white adipose tissue, and whole-body insulin resistance in obese humans. Whether adipose tissue AMPK dysregulation is a causal factor for the development of the inflammation and insulin resistance remains to be determined.

Alternate JournalBiochem Biophys Res Commun
PubMed ID21130749
PubMed Central IDPMC3061625
Grant ListDK067509 / DK / NIDDK NIH HHS / United States
R01 DK19514 / DK / NIDDK NIH HHS / United States
R01 DK019514-30 / DK / NIDDK NIH HHS / United States
R01 DK067509-05 / DK / NIDDK NIH HHS / United States
P01 HL068758 / HL / NHLBI NIH HHS / United States
P01 HL068758-08 / HL / NHLBI NIH HHS / United States
R01 DK019514 / DK / NIDDK NIH HHS / United States
R01 DK067509 / DK / NIDDK NIH HHS / United States
P01-HL68758 / HL / NHLBI NIH HHS / United States