azilsartan and Obesity

Topics: Albuminuria; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Benzimidazoles; Blood Pressure; Diabetes Mellitus, Type 2; Disease Models, Animal; Humans; Hypertension; Insulin Resistance; Obesity; Oxadiazoles

An association between the loss of skeletal muscle mass and obesity in the geriatric population has been identified as a disease known as sarcopenic obesity. Therefore, therapeutic/preventive interventions are needed to ameliorate sarcopenia. The present study investigates the effect of azilsartan (AZL) on skeletal muscle loss in High-Fat Diet (HFD)-induced sarcopenic obese (SO) rats. Four- and fourteen-months male Sprague Dawley rats were used and randomized in control and azilsartan treatment. 14 months animals were fed with HFD for four months and labeled as HFD-fed SO rats. Young & old rats received 0.5% carboxymethyl cellulose as a vehicle/AZL (8 mg/kg, per oral) treatment for six weeks. Grip strength and body composition analysis were performed after the last dose of AZL. Serum and gastrocnemius (GN)muscles were collected after animal sacrifice. AZL treatment significantly increased lean muscle mass, grip strength, myofibrillar protein, and antioxidant (superoxide dismutase & nitric oxide) levels in SO rats. AZL also restored the muscle biomarkers (creatine kinase, myostatin & testosterone), and insulin levels. AZL improves cellular, and ultracellular muscle structure and prevents type I to type II myofiber transitions in SO rats. Further, immunohistochemistry results showed increased expressions of pAkt and reduced expression of MuRF-1 and TNF-α exhibiting that AZL intervention could decrease protein degradation in SO rats. In conclusion, present results showed that AZL significantly increased lean mass, and restored muscle biomarkers, and muscle architecture. Taken together, the aforementioned findings suggest that azilsartan could be a possible therapeutic approach to reduce muscle wasting in sarcopenic obesity.

Topics: Aged; Animals; Diet, High-Fat; Humans; Insulin Resistance; Male; Muscle, Skeletal; Obesity; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Sarcopenia

Hypertension often coexists with insulin resistance. However, most metabolic effects of the antihypertensive agents have been investigated in nomotensive animals, in which different conclusions may arise. We investigated the metabolic effects of the new angiotensin II type 1 receptor blocker azilsartan using the obese Koletsky rats superimposed on the background of the spontaneously hypertensive rats.. Male Koletsky rats were treated with azilsartan (2 mg/kg/day) over 3 weeks. Blood pressure was measured by tail-cuff. Blood biochemical and hormonal parameters were determined by enzymatic or ELISA methods. Gene expression was assessed by RT-PCR.. In Koletsky rats, azilsartan treatment lowered blood pressure, basal plasma insulin concentration and the homeostasis model assessment of insulin resistance index, and inhibited over-increase of plasma glucose and insulin concentrations during oral glucose tolerance test. These effects were accompanied by decreases in both food intake and body weight (BW) increase. Although two treatments showed the same effect on BW gain, insulin sensitivity was higher after azilsartan treatment than pair-feeding. Azilsartan neither affected plasma concentrations of triglyceride and free fatty acids, nor increased adipose mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ and its target genes such as adiponectin, aP2. In addition, azilsartan downregulated 11β-hydroxysteroid dehydrogenase type 1 expression.. These results show the insulin-sensitizing effect of azilsartan in obese Koletsky rats. This effect is independent of decreases in food intake and BW increase or of the activation of adipose PPARγ. Our findings indicate the possible usefulness of azilsartan in the treatment of metabolic syndrome.

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Blood Glucose; Blood Pressure; Enzyme-Linked Immunosorbent Assay; Hypertension; Insulin; Insulin Resistance; Male; Obesity; Oxadiazoles; Polymerase Chain Reaction; PPAR gamma; Rats; Rats, Inbred SHR