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Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice
V B Kumar1, A E Bernardo, K Vyas
1Geriatric Research, Education and Clinical Center, VA Medical Center, St. Louis, MO 63125, USA.
Abstract:
Genetically obese (ob/ob) mice were employed for the study of the effect of metformin on activity and expression of nitric oxide synthase (NOS ) in vitro and in vivo. For in vitro analysis, mouse liver extracts were used. For the in vivo study, (ob/ob) and their control litter mates (ob/c) mice were injected with specified amounts of metformin and the expression of NOS in the adipose tissue and hypothalamus was measured by Western blotting. Results show that metformin exhibited a biphasic effect on NOS activity in vitro. Expression of metformin was differentially altered in the hypothalamus and adipose tissues of the normal and ob/ob animals that were treated with metformin. Further, a significant decrease in food intake occurred in the (ob/ob) mice that received metformin. This decrease in food intake was not accompanied by changes in serum glucose. At inhibitory concentrations, hypothalamic NOS expression changes differentially in normal and ob/ob mice. In normal mice, metformin stimulated NOS expression, while in ob/ob mice there was an inhibition. NOS expression increased in brown adipose tissue of metformin treated control mice, while no such increase was observed in ob/ob mice. No effect of metformin was observed in white adipose tissue of control or obese mice. Thus, metformin may produce anorectic effects through modulation of NOS.
Insights
Metformin affects nitric oxide synthase (NOS) activity and expression in obese mice, leading to reduced food intake. This suggests metformin may reduce appetite by influencing NOS.
Area of Science:
- Biochemistry
- Pharmacology
- Physiology
Background:
- Obesity is a complex metabolic disorder.
- Nitric oxide synthase (NOS) plays a role in metabolic regulation.
- Metformin is a common anti-diabetic drug with potential weight-loss effects.
Purpose of the Study:
- To investigate the effect of metformin on NOS activity and expression in vitro and in vivo.
- To determine the role of NOS in metformin-induced anorectic effects in genetically obese mice.
Main Methods:
- In vitro analysis using mouse liver extracts.
- In vivo study involving metformin administration to obese (ob/ob) and control (ob/c) mice.
- Measurement of NOS expression in adipose tissue and hypothalamus via Western blotting.
Main Results:
- Metformin demonstrated a biphasic effect on NOS activity in vitro.
- Metformin differentially altered NOS expression in the hypothalamus and adipose tissues.
- Obese mice treated with metformin showed a significant decrease in food intake without changes in serum glucose.
- Hypothalamic NOS expression was stimulated by metformin in normal mice but inhibited in obese mice.
- NOS expression increased in brown adipose tissue of control mice but not in obese mice.
Conclusions:
- Metformin's anorectic effects may be mediated through the modulation of nitric oxide synthase.
- Differential regulation of NOS in the hypothalamus and adipose tissue contributes to metformin's effects in obesity.
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