Increased PUFA Content and 5-Lipoxygenase Pathway Expression Are Associated with Subcutaneous Adipose Tissue Inflammation in Obese Women with Type 2 Diabetes.

Obese women with type 2 diabetes mellitus (T2DM) have more inflammation in their subcutaneous white adipose tissue (sWAT) than age-and-BMI similar obese women with normal glucose tolerance (NGT). We aimed to investigate whether WAT fatty acids and/or oxylipins are associated with the enhanced inflammatory state in WAT of the T2DM women. Fatty acid profiles were measured in both subcutaneous and visceral adipose tissue (vWAT) of 19 obese women with NGT and 16 age-and-BMI similar women with T2DM. Oxylipin levels were measured in sWAT of all women. Arachidonic acid (AA) and docosahexaenoic acid (DHA) percentages were higher in sWAT, but not vWAT of the T2DM women, and AA correlated positively to the gene expression of macrophage marker CD68. We found tendencies for higher oxylipin concentrations of the 5-LOX leukotrienes in sWAT of T2DM women. Gene expression of the 5-LOX leukotriene biosynthesis pathway was significantly higher in sWAT of T2DM women. In conclusion, AA and DHA content were higher in sWAT of T2DM women and AA correlated to the increased inflammatory state in sWAT. Increased AA content was accompanied by an upregulation of the 5-LOX pathway and seems to have led to an increase in the conversion of AA into proinflammatory leukotrienes in sWAT.

Resting-state functional connectivity of brain regions involved in cognitive control, motivation, and reward is enhanced in obese females.

BACKGROUND: The brain is crucial for the control of food intake, reward, and energy homeostasis. OBJECTIVE: We hypothesized that 1) brain circuits involved in energy homeostasis and reward show different functional connectivity patterns between obese and lean individuals and 2) food intake affects functional connectivity differentially in obese and lean individuals. Therefore, we compared the connectivity of the hypothalamus, amygdala, and posterior cingulate cortex, each probing a distinct network related to energy homeostasis and reward, between obese subjects and lean subjects in the fasting state and after meal ingestion. DESIGN: We acquired 3 Tesla resting-state functional magnetic resonance imaging scans after an overnight fast and after ingestion of a liquid mixed meal in 46 obese female participants [19 with normal glucose tolerance and 27 with type 2 diabetes mellitus (T2DM)] and 12 lean subjects. Functional connectivity of our regions of interest was assessed by using a seed-based correlation approach. RESULTS: No significant differences between normal-glucose-tolerant and T2DM subjects were observed. In the fasting state, the total obese group had stronger hypothalamic connectivity with the medial prefrontal cortex and the dorsal striatum than did the lean subjects. The amygdala was differentially connected to the right insula in obese compared with lean subjects. Food intake dampened hypothalamic connectivity with the frontal regions in lean subjects, whereas these connections were barely affected in obese subjects. CONCLUSIONS: Our results indicate that functional connectivity in several brain networks, particularly the homeostatic and cognitive control network and the reward network, was different between obese and lean subjects. In the fasting state, obesity appears to be associated with stronger functional connectivity between brain areas involved in cognitive control, motivation, and reward, whereas these connections are largely unaffected by food intake in obese compared with lean subjects.