The brain renin-angiotensin system plays a crucial role in regulating body weight in diet-induced obesity in rats

BACKGROUND AND PURPOSE: Recent studies indicate that reduced weight gain after AT1 blocker treatment may involve a brain-related mechanism. Here we investigated the role of the brain renin-angiotensin system (RAS) on weight regulation and food behavior in the absence or presence of telmisartan. METHODS: Transgenic rats (TGR(ASrAOGEN)) with a brain-specific angiotensinogen deficiency and Sprague Dawley (SD) rats were fed (3 months) with a high-calorie cafeteria diet (CD) or standard chow. Simultaneously to CD feeding, we also treated SD rats and TGR(ASrAOGEN) with telmisartan (8 mg•kg(-1)•d(-1), 3 months). RESULTS: Compared to SD rats, TGR(ASrAOGEN) 1.) had lower weights during chow feeding; 2.) did not become obese during CD feeding; 3.) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD; 4.) showed a reduced energy intake; 5.) had a higher, strain-dependent energy expenditure which is additionally enhanced during CD feeding; 6.) had enhanced mRNA levels of pro-opiomelanocortin; and 7.) showed improved glucose control. Regarding the potency of AT1 receptor blockade on weight regulation, weight gain and energy intake were markedly reduced by telmisartan in SD rats but only to a minor degree in TGR(ASrAOGEN) when animals were simultaneously fed with CD. CONCLUSIONS: The brain RAS has impact on body weight regulation, feeding behavior, and metabolic disorders. When AngII levels are low in brain, rats are protected from developing diet-induced obesity and obesity-related metabolic impairments. We further suggest that telmisartan at least partially lowers body weight via a CNS-driven mechanism.