Decreased AMP-activated protein kinase activity is associated with increased inflammation in visceral adipose tissue and with whole-body insulin resistance in morbidly obese humans.
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.
Diabetes and Metabolism Unit, Section of Endocrinology, Boston University School of Medicine, Boston, MA 02118, USA. ms.gauthier@gmail.com
Marie-Soleil
MS
Gauthier
Elena L
EL
O'Brien
Sherman
S
Bigornia
Melanie
M
Mott
Jose M
JM
Cacicedo
X Julia
XJ
Xu
Noyan
N
Gokce
Caroline
C
Apovian
Neil
N
Ruderman
D055372:AMP-Activated Protein Kinases / Q000032:analysis / Q000378:metabolism*; D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000201:enzymology*
D015415:Biomarkers; D055372:AMP-Activated Protein Kinases