Impaired diet-induced thermogenesis in brown adipose tissue from rats made obese with parasagittal hypothalamic knife-cuts

Abstract

Two experiments were performed to determine if bilateral parasagittal hypothalamic knife-cuts (KCs), which produce long-term overeating and obesity, alter biochemical indices of brown adipose tissue (BAT) reactivity to thermogenic stimuli. In the first study, responses to environmental cold were tested. Four weeks after surgery, KC rats had gained 4–5 times more weight than controls and were obese (increased Lee Obesity Index and weight of gonadal white fat). Before being sacrificed, groups of KC and control rats were exposed to 4°C for 21 hr or remained at 28°C. Interscapular BAT weighed 300% more in KC rats, due largely to increased white fat content. Functional indices of BAT thermogenic capacity (protein content, DNA content, cytochrome oxidase activity and mitochondrial guanosine diphosphate (GDP) binding) were normal at 28°C. Exposure to 4°C produced greatly enhanced responses but these were equivalent for both groups. This suggested an intact capacity for non-shivering thermogenesis in obese KC rats. In the second study, the same BAT responses were examined in other rats fed a palatable “cafeteria” diet (CAFE). One week after surgery, KC and control rats were subdivided into groups that received chow alone or chow plus four different palatable foods daily. Before sacrificing 4–5 weeks later, KC rats had gained 3–4 times more weight than controls and were obese. Interscapular BAT weighed 200–300% more in KC rats. CAFE feeding produced larger increments in all variables for KC vs. control rats. Most importantly, GDP binding was reduced in both KC groups, and significantly more so after CAFE feeding. Furthermore, CAFE feeding failed to elicit the usual increase in serum concentration of triiodothyronine after KC. Pair-feeding KC rats control levels of chow largely prevented all of these abnormalities. These results suggest that BAT from KC-obese rats maintains normal thermogenic reactivity to cold but not to high-calorie foods. These findings parallel almost exactly previous observations in rats made obese by medial hypothalamic lesions. Viewed collectively, they imply that the neural and/or hormonal controls over BAT are different in response to these two thermogenic stimuli.