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Measurement of nitric oxide synthase and its mRNA in genetically obese (ob/ob) mice
J E Morley1, V B Kumar, M Mattammal
1Geriatric Research, Education and Clinical Center, St. Louis VA Medical Center, MO, USA.
Abstract:
Recent studies have suggested a role for nitric oxide (NO) in the regulation of food intake. The obese (ob/ob) mouse is a genetic model of obesity. Previously, it has been demonstrated that ob/ob mice show a marked weight reduction when treated with a nitric oxide synthase inhibitor. In the studies reported here, we demonstrate increased levels of nitric oxide synthase (NOS) and its mRNA in the hypothalamus of genetically obese (ob/ob) mice compared to their lean littermate controls (ob/c). NOS levels were 0.016 +/- 0.001 nmol/mg/min in ob/ob compared to 0.009 +/- 0.001 in ob/c (p < 0.01) and NOS mRNA was 32.0 +/- 5.0 pg NOS mRNA/mg total RNA in ob/ob compared to 12.4 +/- 4.0 in ob/c (p < 0.05). These studies further support the possibility of a role for nitric oxide in the regulation of food intake.
Insights
Genetically obese mice exhibit higher levels of nitric oxide synthase (NOS) and its messenger RNA (mRNA) in the hypothalamus. This finding suggests nitric oxide plays a role in regulating food intake and obesity.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Molecular Biology
Background:
- Nitric oxide (NO) is implicated in regulating food intake.
- Obese (ob/ob) mice are a genetic model for obesity.
- Nitric oxide synthase (NOS) inhibitors reduce weight in ob/ob mice.
Purpose of the Study:
- To investigate the role of nitric oxide synthase (NOS) in the hypothalamus of genetically obese (ob/ob) mice.
- To compare NOS and its mRNA levels in ob/ob mice versus lean controls (ob/c).
Main Methods:
- Quantitative analysis of NOS activity in hypothalamic tissue.
- Measurement of NOS mRNA levels using established molecular biology techniques.
Main Results:
- Ob/ob mice displayed significantly increased NOS levels (0.016 +/- 0.001 nmol/mg/min) compared to ob/c mice (0.009 +/- 0.001 nmol/mg/min, p < 0.01).
- NOS mRNA levels were also elevated in ob/ob mice (32.0 +/- 5.0 pg/mg total RNA) relative to ob/c mice (12.4 +/- 4.0 pg/mg total RNA, p < 0.05).
Conclusions:
- The hypothalamus of obese mice shows increased nitric oxide synthase (NOS) expression and activity.
- These findings support a role for nitric oxide in the regulation of appetite and the development of obesity.