title: Expression of FOXC2 in adipose and muscle and its association with whole body insulin sensitivity.
abstract: FOXC2 is a winged helix/forkhead transcription factor involved in PKA signaling. Overexpression of FOXC2 in the adipose tissue of transgenic mice protected against diet-induced obesity and insulin resistance. We examined the expression of FOXC2 in fat and muscle of nondiabetic humans with varying obesity and insulin sensitivity. There was no relation between body mass index (BMI) and FOXC2 mRNA in either adipose or muscle. There was a strong inverse relation between adipose FOXC2 mRNA and insulin sensitivity, using the frequently sampled intravenous glucose tolerance test (r = -0.78, P < 0.001). However, there was no relationship between muscle FOXC2 and any measure of insulin sensitivity. To separate insulin resistance from obesity, we examined FOXC2 expression in pairs of subjects who were matched for BMI but who were discordant for insulin sensitivity. Compared with insulin-sensitive subjects, insulin-resistant subjects had threefold higher levels of adipose FOXC2 mRNA (P = 0.03). In contrast, muscle FOXC2 mRNA expression was no different between insulin-resistant and insulin-sensitive subjects. There was no association of adipose or muscle FOXC2 mRNA with either circulating or adipose-secreted TNF-alpha, IL-6, leptin, adiponectin, or non-esterified fatty acids. Thus adipose FOXC2 is more highly expressed in insulin-resistant subjects, and this effect is independent of obesity. This association between FOXC2 and insulin resistance may be related to the role of FOXC2 in PKA signaling.
authors.affiliation: The Central Arkansas Veterans Healthcare System, Department of Medicine, Little Rock 72205, USA. digregorioginab@uams.edu
authors.forename: Gina B
authors.initials: GB
authors.lastname: Di Gregorio
authors.forename: Rickard
authors.initials: R
authors.lastname: Westergren
authors.forename: Sven
authors.initials: S
authors.lastname: Enerback
authors.forename: Tong
authors.initials: T
authors.lastname: Lu
authors.forename: Philip A
authors.initials: PA
authors.lastname: Kern
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016207:Cytokines; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein