Obesity is associated with altered mid-insula functional connectivity to limbic regions underlying appetitive responses to foods

Obesity is fundamentally a disorder of energy balance. In obese individuals, more energy is consumed than is expended, leading to excessive weight gain through the accumulation of adipose tissue. Complications arising from obesity, including cardiovascular disease, elevated peripheral inflammation, and the development of Type II diabetes, make obesity one of the leading preventable causes of morbidity and mortality. Thus, it is of paramount importance to both individual and public health that we understand the neural circuitry underlying the behavioral regulation of energy balance. To this end, we sought to examine obesity-related differences in the resting state functional connectivity of the dorsal mid-insula, a region of gustatory and interoceptive cortex associated with homeostatically sensitive responses to food stimuli. Within the present study, obese and healthy weight individuals completed resting fMRI scans during varying interoceptive states, both while fasting and after a standardized meal. We examined group differences in the pre- versus post-meal functional connectivity of the mid-insula, and how those differences were related to differences in self-reported hunger ratings and ratings of meal pleasantness. Obese and healthy weight individuals exhibited opposing patterns of eating-related functional connectivity between the dorsal mid-insula and multiple brain regions involved in reward, valuation, and satiety, including the medial orbitofrontal cortex, the dorsal striatum, and the ventral striatum. In particular, healthy weight participants exhibited a significant positive relationship between changes in hunger and changes in medial orbitofrontal functional connectivity, while obese participants exhibited a complementary negative relationship between hunger and ventral striatum connectivity to the mid-insula. These obesity-related alterations in dorsal mid-insula functional connectivity patterns may signify a fundamental difference in the experience of food motivation in obese individuals, wherein approach behavior toward food is guided more by reward-seeking than by homeostatically relevant interoceptive information from the body.