Effect of metformin on nitric oxide synthase in genetically obese (ob/ob) mice.
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.
Kumar
V B
VB
Geriatric Research, Education and Clinical Center, VA Medical Center, St. Louis, MO 63125, USA.
Bernardo
A E
AE
Vyas
K
K
Franko
M
M
Farr
S
S
Lakshmanan
L
L
Buddhiraju
C
C
Morley
J E
JE
D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000201:enzymology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008820:Mice, Obese; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D014020:Tissue Extracts; D015430:Weight Gain / Q000187:drug effects
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D014020:Tissue Extracts; D008687:Metformin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse