Influence of AT1 blockers on obesity and stress-induced eating of cafeteria diet

Abstract

Journal of Endocrinology240:1 65-79 V Gustaityte et al. ARB and stress eating of cafeteria diet AbstractBased on findings that treatment with AT 1 receptor blocker (ARB) prevents dietinduced obesity and that the activity of the hypothalamic-pituitary-adrenal (HPA) axis is stimulated by AngII and blocked by ARBs, we aimed to investigate whether ARB treatment can reduce stress-induced eating of cafeteria diet (CD), thus contributing to alterations in eating behavior. Sprague-Dawley rats were fed with chow or CD and treated with telmisartan (TEL, 8 mg/kg/day) or vehicle. At weeks 2 and 12, rats were stressed over five consecutive days by restraint stress (RS, 4 h) and by additional shaking at d5. Tail blood was sampled during RS to determine hormone levels. During the first period of RS, ACTH and corticosterone responses were diminished at d5 in CD-compared to chow-fed rats. Independently of feeding, TEL did not reduce stress hormones. Compared to food behavior before RS, the stress-induced CD eating increased in controls but remained unchanged in TEL-treated rats. After 12 weeks, TEL reduced weight gain and energy intake, particularly in CD-fed rats. Similar to the first RS period, corticosterone response was reduced in CD-fed rats at d5 during the second RS period. TEL did not further reduce stress hormones and did not lessen the CD eating upon RS. We conclude that CD feeding compensates for stress reactions. However, stress-induced CD eating was only reduced by TEL after short term, but not after longterm drug treatment. Thus, the potency of ARBs to lower HPA activity only plays a minor role in reducing energy intake to prevent obesity.

Telmisartan prevents development of obesity and normalizes hypothalamic lipid droplets

“…Once a day, mice received TEL (8 mg/kg bw ) or vehicle by oral gavage in a volume of 5 µL/g body weight. TEL dosages were evaluated recently (Muller-Fielitz et al 2012) and have been confirmed in numerous studies both in rats (Miesel et al 2012, Muller-Fielitz et al 2014, Schuchard et al 2015, Winkler et al 2016, Gustaityte et al 2018 and in mice (Schuster et al 2018, Dapper et al 2019 to reveal antiobese effects. For administration, TEL was suspended in 10% gum arabic (Carl Roth GmbH, Karlsruhe, Germany), resulting in a suspension of 1.6 mg/mL TEL.…”

“…We finally investigated whether the potency of ARBs to reduce the drive of the hypothalamic-pituitary-adrenal (HPA) axis contributes to a decrease in food intake. However, we recently demonstrated that stress-induced eating of high-calorie, good-tasting food only plays a minor role or none at all (Gustaityte et al 2018). As outlined in the introduction, the antiobese effect of ARBs is dependent on intact leptin signaling and leptin penetration across the BBB.…”

The AT1 Receptor Blocker Telmisartan Reduces Intestinal Mucus Thickness in Obese Mice

“…Once a day, mice received TEL (8 mg/kg bw ) or vehicle by oral gavage in a volume of 5 µL per gram body weight (bw) according to previous studies ( Schuster et al, 2018 ; Dapper et al, 2019 ; Rawish et al, 2020 ). TEL dosage was recently evaluated ( Muller-Fielitz et al, 2012 ) and has been confirmed in numerous studies both in rats ( Miesel et al, 2012 ; Muller-Fielitz et al, 2014 ; Muller-Fielitz et al, 2015 ; Schuchard et al, 2015 ; Winkler et al, 2016 ; Gustaityte et al, 2019 ) and in mice ( Schuster et al, 2018 ; Dapper et al, 2019 ; Rawish et al, 2020 ; Huber et al, 2021 ) to reveal anti-obese effects. For administration, TEL was suspended in 10% gum arabic (Carl Roth GmbH, Karlsruhe, Germany), resulting in a suspension of 1.6 mg/ml TEL.…”

“…Thus, AngII receptor (type 1) blockers (ARBs) such as telmisartan (TEL) and losartan (LOS) are well-established in the treatment of hypertension and heart failure, particularly with regard to their cardiometabolic benefits ( Michel et al, 2016 ). Beyond these beneficial actions, ARBs have been demonstrated to preventively and curatively lower obesity in rodents ( Muller-Fielitz et al, 2011 ; Miesel et al, 2012 ; Muller-Fielitz et al, 2012 ; Muller-Fielitz et al, 2014 ; Muller-Fielitz et al, 2015 ; Schuchard et al, 2015 ; Schuster et al, 2018 ; Winkler et al, 2018 ; Gustaityte et al, 2019 ; Rawish et al, 2020 ; Huber et al, 2021 ) and humans ( Kintscher et al, 2007 ). The anti-obese potency of ARBs occurs mainly after high dosages and is independent of their ability to reduce blood pressure ( Muller-Fielitz et al, 2011 ; Muller-Fielitz et al, 2014 ).…”

“…We very recently showed that TEL protects against neurovascular unit impairments in a diet-induced obesity setting, which may play a role in preventing obesity-related cognitive deficits, as we demonstrated that TEL treatment normalized high-fat diet-induced reduction of cerebral blood flow and prevented diet-induced anxiety-like behavior and that TEL affects cellular senescence and string vessel formation in obesity ( Huber et al, 2021 ). In addition to these putative mechanisms, an angiotensin-converting enzyme 2 (ACE2)/Ang (1–7)/Mas axis-related mechanism ( Blanke et al, 2015 ; Schuchard et al, 2015 ; Dapper et al, 2019 ) is also involved in ARB-induced weight loss, while the pleiotropic potency of ARBs to stimulate peroxisome proliferator-activated receptor gamma (PPARγ) ( Muller-Fielitz et al, 2012 ; Schuster et al, 2018 ) and the potency of ARBs to lower stress ( Gustaityte et al, 2019 ) play only a minor or no role.…”