Abstract
Increased total fat mass (FM) and visceral fat (VF) may account in part for age-associated decrease in hepatic insulin action. This study determined whether preventing the changes in body fat distribution abolished this defect throughout aging. We studied the F1 hybrid of Brown Norway-Fischer 344 rats (n = 29), which we assigned to caloric restriction (CR) or fed ad libitum (AL). CR (55% of the calories consumed by AL) was initiated and used at 2 mo to prevent age-dependent increases in FM and VF. AL rats were studied at 2, 8, and 20 mo; CR rats were studied at 8 and 20 mo. VF and FM remained unchanged throughout aging in CR rats. AL-fed rats at 8 and 20 mo had over fourfold higher FM and VF compared with both CR groups. Insulin clamp studies (3 mU·kg-1·min-1 with somatostatin) were performed to assess hepatic insulin sensitivity. Prevention of fat accretion resulted in a marked improvement in insulin action in the suppression of hepatic glucose production (HGP) (6.3 ± 0.3 and 7.2 ± 1.2 mg·kg-1·min-1 in 8- and 20- mo CR rats vs. 8.3 ± 0.5 and 10.8 ± 0.9 mg·kg-1·min-1 in 8- and 20-mo AL rats, respectively). The rate of gluconeogenesis (by enrichment of hepatic uridine diphosphate glucose and phosphoenolpyruvate pools by [14C]lactate) was unchanged in all groups. The improvement in hepatic insulin action in the CR group was mostly due to effective suppression of glycogenolysis (4.4 ± 0.3 and 4.9 ± 0.3 mg·kg-1·min-1 in 8- and 20-mo CR rats vs. 5.8 ± 0.6 and 8.2 ± 1.0 mg·kg-1·min-1 in 8- and 20-mo AL rats, respectively). The results demonstrated the preservation of hepatic insulin action in aging CR rats. Therefore, body fat and its distribution are major determinants of age-associated hepatic insulin resistance.
Original language | English (US) |
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Pages (from-to) | E985-E991 |
Journal | American Journal of Physiology - Endocrinology and Metabolism |
Volume | 278 |
Issue number | 6 41-6 |
DOIs | |
State | Published - Jun 2000 |
Keywords
- Caloric restriction
- Obesity
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Physiology (medical)