Insulin sensitive and resistant obesity in humans: AMPK activity, oxidative stress, and depot-specific changes in gene expression in adipose tissue.
We previously reported that adenosine monophosphate-activated protein kinase (AMPK) activity is lower in adipose tissue of morbidly obese individuals who are insulin resistant than in comparably obese people who are insulin sensitive. However, the number of patients and parameters studied were small. Here, we compared abdominal subcutaneous, epiploic, and omental fat from 16 morbidly obese individuals classified as insulin sensitive or insulin resistant based on the homeostatic model assessment of insulin resistance. We confirmed that AMPK activity is diminished in the insulin resistant group. A custom PCR array revealed increases in mRNA levels of a wide variety of genes associated with inflammation and decreases in PGC-1α and Nampt in omental fat of the insulin resistant group. In contrast, subcutaneous abdominal fat of the same patients showed increases in PTP-1b, VEGFa, IFNγ, PAI-1, and NOS-2 not observed in omental fat. Only angiotensinogen and CD4(+) mRNA levels were increased in both depots. Surprisingly, TNFα was only increased in epiploic fat, which otherwise showed very few changes. Protein carbonyl levels, a measure of oxidative stress, were increased in all depots. Thus, adipose tissues of markedly obese insulin resistant individuals uniformly show decreased AMPK activity and increased oxidative stress compared with insulin sensitive patients. However, most changes in gene expression appear to be depot-specific.
Diabetes and Metabolism Unit, Section of Endocrinology, Boston University School of Medicine, Boston, MA 02118, USA.
X Julia
XJ
Xu
Marie-Soleil
MS
Gauthier
Donald T
DT
Hess
Caroline M
CM
Apovian
Jose M
JM
Cacicedo
Noyan
N
Gokce
Melissa
M
Farb
Rudy J
RJ
Valentine
Neil B
NB
Ruderman
D000263:Adenylate Kinase / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007328:Insulin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000808:Angiotensinogen; D000263:Adenylate Kinase