TY - JOUR
T1 - Interaction between aging and Syndrome X
T2 - New insights on the pathophysiology of fat distribution
AU - Barzilai, Nir
AU - Gupta, Gaurav
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1999
Y1 - 1999
N2 - Increased fat mass (FM), and in particular a specific increase in visceral fat (VF), may account for the age-associated decrease in insulin action and the development of Syndrome X. Utilizing chronic caloric restriction (CR) with aging in a rodent model, we dissociated the effects of VF and FM, and demonstrated that the decrease in VF accumulation was sufficient to prevent the marked decrease in hepatic insulin action. This suggests that the typical increase in VF with aging, rather than aging per se, determines hepatic insulin resistance. To directly assess the role of VF, we studied rats after surgical removal of VF or sham operation. Surgical extraction of VF (which accounts for ~ 10% of total fat) improved hepatic insulin action by more than twofold. We studied the role of fat-derived peptides in the regulation of body composition and insulin action. While VF extraction resulted in decreased gene expression for leptin and TNF-α in the subcutaneous adipose, administration of leptin selectively decreased visceral fat (~ 60%), and enhanced the action of insulin on inhibiting hepatic glucose production (~ 80%). Thus, the cause-effect relationship between the age-related increase in VF and the decrease in hepatic insulin action may involve the failure of leptin to 'cross talk' with other fat depots to regulate fat distribution.
AB - Increased fat mass (FM), and in particular a specific increase in visceral fat (VF), may account for the age-associated decrease in insulin action and the development of Syndrome X. Utilizing chronic caloric restriction (CR) with aging in a rodent model, we dissociated the effects of VF and FM, and demonstrated that the decrease in VF accumulation was sufficient to prevent the marked decrease in hepatic insulin action. This suggests that the typical increase in VF with aging, rather than aging per se, determines hepatic insulin resistance. To directly assess the role of VF, we studied rats after surgical removal of VF or sham operation. Surgical extraction of VF (which accounts for ~ 10% of total fat) improved hepatic insulin action by more than twofold. We studied the role of fat-derived peptides in the regulation of body composition and insulin action. While VF extraction resulted in decreased gene expression for leptin and TNF-α in the subcutaneous adipose, administration of leptin selectively decreased visceral fat (~ 60%), and enhanced the action of insulin on inhibiting hepatic glucose production (~ 80%). Thus, the cause-effect relationship between the age-related increase in VF and the decrease in hepatic insulin action may involve the failure of leptin to 'cross talk' with other fat depots to regulate fat distribution.
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U2 - 10.1111/j.1749-6632.1999.tb07785.x
DO - 10.1111/j.1749-6632.1999.tb07785.x
M3 - Article
C2 - 10842652
AN - SCOPUS:0032786470
SN - 0077-8923
VL - 892
SP - 58
EP - 72
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -