Increased susceptibility to insulin resistance associated with abdominal obesity in aging rats.
OBJECTIVE
Recent data have suggested that the insulin resistance observed with aging may be more related to adiposity than aging per se. We asked whether the insulin resistance observed in aged rats was comparable (both in magnitude and location) to that of fat-fed rats.


METHODS
We performed hyperinsulinemic (5 mU/min per kg) euglycemic clamps with tracer in conscious, 6-hour fasted young (YL), fat-fed young (YF), fat-fed old (OF), and calorically restricted old (OL) rats.


RESULTS
Intraabdominal fat measurements showed that OF and YF rats were more obese than YL (p<or=0.001; YF>OF>YL). Caloric restriction not only prevented age-related obesity but also reduced the ratio of intraabdominal fat to lean body mass (LBM) compared with YL (OL: 0.59+/-0.05 vs. YL: 1.07+/-0.04; p=0.017). Despite similar incremental insulin, YF and OF rats required 40% less infused glucose to maintain euglycemia than YL and OL rats (p<0.001). Insulin-stimulated glucose uptake (Si(Rd): DeltaRd/(DeltaInsulin x Glucose(SS)) was impaired in OF rats (OF: 14.03+/-1.79 vs. YL: 23.08+/-1.87x10(3) dL/min x kg LBM per pM; p=0.004) and improved in OL rats (29.41+/-1.84x10(3) dL/min x kg LBM per pM; p=0.031) compared with YL. Despite greater obesity, YF rats did not exhibit lower SiRd compared with OF rats (p=0.58). In contrast, the ability of insulin to suppress endogenous glucose production (EGP; Si(EGP): DeltaEGP/(DeltaInsulin x GlucoseSS) was not impaired in OF rats (OF vs. YL; p=0.61) but was markedly impaired in YF rats by approximately 75% (1.72+/-0.66x10(3) dL/min x kg per pM; p=0.013). Surprisingly, separate regression analysis for old and young animals revealed that old rats exhibited a significantly steeper regression between Si (Rd and EGP) and adiposity than young rats (p<0.05). Thus, older rats showed a proportionately greater decrement in insulin sensitivity with an equivalent increase in adiposity.


CONCLUSIONS
These data suggest that, in rodents, youth affords significant protection against obesity-induced insulin resistance.
Catalano
Karyn J
KJ
Department of Physiology and Biophysics, University of Southern California Keck School of Medicine, 1333 San Pablo St., MMR 624, Los Angeles, CA 90033, USA.
Bergman
Richard N
RN
Ader
Marilyn
M
D000005:Abdomen / Q000473:pathology; D000273:Adipose Tissue / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D004041:Dietary Fats / Q000378:metabolism; D004435:Eating / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005508:Food Deprivation / Q000502:physiology; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344
D001786:Blood Glucose; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin