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In adults with obesity, brain insulin action may be selectively impaired
The prefrontal cortexes of adults with overweight and obesity appear to have selectively impaired brain insulin action, possibly causing a modified homeostatic set point and decreased control of overeating behaviors, according to recent findings.
Likewise, the hypothalamus of adults with high visceral adipose tissue may be impaired in terms of brain insulin action, according to the researchers.
“To date, the central nervous effects of insulin in obese humans still remain ill-defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance,” the researchers wrote. “We hypothesized that overweight and obese adults will show cerebral insulin resistance in regions associated with food intake and eating behavior.”
In the study, Stephanie Kullman, PhD, of the University of Tübingen in Germany, and colleagues evaluated 25 healthy lean adults, 10 adults with overweight and 13 adults with obesity who were students at the University of Tübingen.
Prior to the start of the study, all participants were examined to rule out psychiatric, neurologic and metabolic disease, and a 75-g oral glucose tolerance test (OGTT) was conducted to rule out diabetes. Body fat distribution was evaluated through whole-body MRI tests, which quantified body volume, total adipose tissue and total mass of specific depots, such as visceral adipose tissue.
After the OGTT and whole-body MRI tests, participants received an intranasal insulin or placebo, on two separate days between 4 and 14 days apart. Cerebral blood flow was evaluated before and 30 minutes after intranasal insulin or placebo. In addition, participants rated desirability of pictures of high-calorie savory and sweet foods 60 minutes after the spray was administered.
The researchers found that in response to the insulin vs. placebo, there was a significant decrease in cerebral blood flow in the hypothalamus of lean participants and those with overweight or obesity. Independent of other fat components, the extent of this decrease corresponded with higher visceral adipose tissue.
Moreover, the response in the prefrontal cortex differed between lean participants and those with overweight or obesity, leading to insulin-triggered cerebral blood flow reduction in lean participants only. The response in the prefrontal cortex was significantly associated with peripheral insulin sensitivity and measures of eating behavior, including disinhibition and food craving.
Post hoc analyses revealed, in men only, a significant difference between lean participants and those with obesity in terms of cravings for sweet foods; after insulin was given, lean men demonstrated a significant decrease in wanting sweet foods (P = .01).
According to the researchers, the suppression of the hypothalamus and the prefrontal cortex may be associated with increased satiety and a reduced response to food, thus explaining the decreased craving for sweet foods in lean men.
“Obesity, however, dampens this attenuation, promoting an altered homeostatic set point and potentially reducing the inhibitory control contributing to overeating behavior,” the researchers wrote. “The identification of hormone-brain interactions that modulate food intake can potentially aid in the development of effective obesity therapies.” – by Jennifer Byrne
Disclosure: The researchers report no relevant financial disclosures.