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

M Winkler, J Schuchard, I Stölting… - British journal of …, 2016 - Wiley Online Library
M Winkler, J Schuchard, I Stölting, FM Vogt, J Barkhausen, C Thorns, M Bader, W Raasch
British journal of pharmacology, 2016Wiley Online Library
Background and Purpose Reduced weight gain after treatment with AT1 receptor
antagonists may involve a brain‐related mechanism. Here, we investigated the role of the
brain renin‐angiotensin system on weight regulation and food behaviour, with or without
additional treatment with telmisartan. Methods Transgenic rats with a brain‐specific
deficiency in angiotensinogen (TGR (ASrAOGEN)) and the corresponding wild‐type,
Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or …
Background and Purpose
Reduced weight gain after treatment with AT1 receptor antagonists may involve a brain‐related mechanism. Here, we investigated the role of the brain renin‐angiotensin system on weight regulation and food behaviour, with or without additional treatment with telmisartan.
Methods
Transgenic rats with a brain‐specific deficiency in angiotensinogen (TGR(ASrAOGEN)) and the corresponding wild‐type, Sprague Dawley (SD) rats were fed (3 months) with a high‐calorie cafeteria diet (CD) or standard chow. SD and TGR(ASrAOGEN) rats on the CD diet were also treated with telmisartan (8 mg·kg−1·d−1, 3 months).
Results
Compared with SD rats, TGR(ASrAOGEN) rats (i) had lower weights during chow feeding, (ii) did not become obese during CD feeding, (iii) had normal baseline leptin plasma concentrations independent of the feeding regimen, whereas plasma leptin of SD rats was increased due to CD, (iv) showed a reduced energy intake, (v) had a higher, strain‐dependent energy expenditure, which is additionally enhanced during CD feeding, (vi) had enhanced mRNA levels of pro‐opiomelanocortin and (vii) showed improved glucose control. Weight gain and energy intake in rats fed the CD diet were markedly reduced by telmisartan in SD rats but only to a minor extent in TGR(ASrAOGEN) rats.
Conclusions
The brain renin‐angiotensin system affects body weight regulation, feeding behaviour and metabolic disorders. When angiotensin II 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 partly lowers body weight via a CNS‐driven mechanism.
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