The Elucidation of the Mechanism of Weight Gain and Glucose Tolerance Abnormalities Induced by Chlorpromazine

Abstract

Abstract. Antipsychotic drugs induce weight gain and metabolic abnormalities. Recently, the role of adipocytokines secreted from adipocytes in the development of metabolic syndrome has received attention. The aim of this study was to investigate the effects of chlorpromazine (Cp) on body weight, glucose, lipid metabolism, and adipocytokine secretion in rats fed sucrose. Wistar rats received 15% sucrose (Suc group), 15% sucrose and Cp at 7.5 mg / kg per day (Suc + Cp group), or Cp alone (Cp group) in water for 10 weeks. Fasting glucose levels in the Suc and Suc + Cp groups were significantly higher than in the control (Cont) group. Fasting insulin levels in the Suc, Suc + Cp, and Cp groups were also significantly higher than in the Cont group. The adiponectin level in the Suc group was significantly higher than in the Cont group, although the adiponectin level in the Suc + Cp group was not. Furthermore, the plasma tumor necrosis factor (TNF)-α level in the Suc + Cp group was significantly higher than in the Suc group. These data suggest that Cp inhibits the compensatory response of adiponectin with respect to obesity due to increased expression of plasma TNF-α level. Cp may exert more harmful effects on the glucose level and insulin resistance than on other factors, which may be one of the mechanisms responsible for the metabolic syndrome induced by antipsychotic agents.

Weight Gain and Metabolic Abnormalities During Extended Risperidone Treatment in Children and Adolescents

“…Insulin resistance could ensue secondary to weight gain, change in body fat composition, or could be due to a direct effect of the antipsychotics on insulin sensitivity (American Diabetes Association 2004; Amamoto et al 2006). Data are again scant in children and adolescents.…”

Effects of Pioglitazone on Increases in Visceral Fat Accumulation and Oxidative Stress in Spontaneously Hypertensive Hyperlipidemic Rats Fed a High-Fat Diet and Sucrose Solution

“…Since visceral fat tissue secretes various physiologically active substances, we determined plasma IL-6 levels, but there was no significant increase in the HFDS-SHHR compared to the SHHR-control and HFDS-SD. Amamoto et al reported that Wister rats that ingested a 15% sucrose solution for 10 weeks showed a significant increase in visceral fat weight with increases in plasma blood glucose, insulin, leptin, and adiponectin, but not plasma TNF-α and IL-6 (27). Therefore, a further experiment to determine other adipocytokines is necessary.…”

Effects of Antipsychotic Medications on Appetite, Weight, and Insulin Resistance

“…11,49,69,70 Since they were introduced to the clinics in the 1950s, chlorpromazine and thioridazine have been repeatedly reported to cause abnormal glucose tolerance, insulin resistance and even T2DM. [70][71][72][73][74][75][76] On the other hand, it was generally believed that haloperidol did not increase the risk of insulin resistance and T2DM, 49 however recent evidence from clinical trials in first episode patients showed that haloperidol may have a higher risk than originally thought. As discussed above, the EUFEST study has reported that one year treatment of haloperidol has a similar incident rate of hyperglycemia and increased fasting insulin levels to atypical APDs olanzapine and quetiapine.…”