PS 10-01 SIGNIFICANCE OF RENAL AUTONOMIC NERVES FOR BODY WEIGHT REDUCTION-BY TOFOGLIFLOZIN

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Abstract

Objective:

Sodium-glucose co-transporter (SGLT) 2 inhibitors decrease not only serum glucose level but also the body weight significantly. However, the mechanism responsible for the weight reduction has not been elucidated. Renal denervation (RDN) is also reported to affect the body weight. Therefore, we speculated that renal autonomic nerves might be involved in the mechanism by which SGLT2 inhibitors reduces the body weight. The present study examined whether RDN affects the weight reduction by a SGLT2 inhibitor, by using diet-induced obese mice treated with a SGLT2 inhibitor, tofogliflozin (tofo).

Design and Method:

The C57bl/6 mice fed on a high-fat diet were divided into 4 groups; control, RDN, SGLT2 inhibitor (tofo) and tofo with RDN groups. We measured the body weight, the systolic blood pressure and the glucose tolerance. The SGLT2 inhibitor was administered to mice from 8 to 16 weeks old by mixing it in the high-fat diet (tofogliflozin 5 mg/g pellet, 60 Kcal% fat). RDN was performed at 7 weeks old by surgically stripping renal arteries and coating the vessels with a solution of 10% phenol in ethanol.

Results:

The body weight at 16 weeks old significantly decreased in tofo group. In that group, catecholamine levels and activity of hormone sensitive lipase (HSL) in the adipose tissue were increased. On the other hand, RDN significantly weakened the degree of body weight reduction by a treatment with tofogliflozin associated with suppression of the catecholamine levels and HSL activity. In RDN without tofo group, the body weight slightly decreased; however, the HSL activity was not changed.

Conclusions:

These results indicated that HSL activation in the adipose tissue by tofogliflozin were affected by the activity of renal autonomic nerves. The renal autonomic nerves would have a role in the control of body weight.

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