An Analysis of the Relationships Among Obesity, Plasma Insulin, and Hepatic Lipogenic Enzymes in "Viable Yellow Obese" Mice (A^vy/a)

Abstract

The development of obesity, hyperinsulinemia and six hepatic lipogenic enzymes in Avy/a mice were compared to that in a/a mice. Correlation between body weight, liver weight, plasma insulin concentration and activities of hepatic enzymes was analyzed. In the Avy/a mice, body weight, liver weight and plasma insulin level increased steadily as the mice aged. In the a/a mice, the change of these three parameters was much slower. Plasma insulin concentration in a/a mice did not increase until eight months of age. Compared with a/a mice, Avy/a mice had higher 6-phosphogluconate dehydrogenase and fatty acid synthetase activities at two months of age; lower citrate cleavage enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities at three months of age; lower citrate cleavage enzyme and glucose-6-phosphate dehydrogenase and higher acetyl CoA carboxylase activities at five months of age; and higher malic enzyme, citrate cleavage enzyme and 6-phosphogluconate dehydrogenase activities at eight months of age. There were significant correlations between plasma insulin level and body weight and between plasma insulin level and the activities of malic enzyme and citrate cleavage enzyme in Avy/a mice. The correlation between body weight and malic enzyme and citrate cleavage enzyme activities disappeared after the analysis was adjusted for plasma insulin level.

Abnormalities of the somatotrophic axis in the obese agouti mouse

“…In accord with previously described results, 31 obese A y /a mice were hyperinsulinaemic (4.370.5 (A y /a) vs 1.970.3 ng/ml (a/a), n ¼ 12-17, Po0.005). Also consistent with previous studies, 32,33 plasma leptin was significantly elevated in obese A y /a mice compared to WT controls (26.674.1 (A y /a) vs 5.370.5 ng/ml (a/a), n ¼ 11-20, Po0.001), reflecting their increased adiposity.…”

Deficiency in Cytosolic Malic Enzyme Does Not Increase Acetaminophen‐Induced Hepato‐Toxicity

“…Due to its concerted induction with glucose-6-phosphate dehydrogenase and 6-phospho-gluconate dehydrogenase, two NADPH producing enzymes important for fatty acid synthesis, ME-1 is also considered a lipogenic enzyme [1][2][3][4][5][6]. Indeed, higher levels of liver ME-1 activity have been associated with obese mouse and rat models [7,8]. High ME-1 activity has also been observed in certain human carcinoma cell lines [9,10], possibly reflecting altered energy metabolism in cancer cells.…”

Rodent Models of Diabetes

“…Similar to the KK mice, obesity is more prominent in male KK-A y mice (Reviewed in [92]). In addition, while KK-A y mice consume between 10% and 36% more calories than their lean littermates [95][96][97], they exhibit some level of satiety [98]. The obesity in these mice has been hypothesized to be due to improved storage of calories as fat [99].…”