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Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats.

Catalano KJ, Stefanovski D, Bergman RN - Diabetes (2010)

Bottom Line: In addition, there was significantly more reversal of fat accumulation in the liver in young (% reduction: 89 +/- 2) versus old (64 +/- 5) rats (P < 0.0001).These results suggest a singular role for mesenteric fat to determine insulin resistance.This role may be related to delivery of lipid to liver, and associated accumulation of liver fat.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.

ABSTRACT

Objective: Age-associated insulin resistance may be caused by increased visceral adiposity and older animals appear to be more susceptible to obesity-related resistance than young animals. However, it is unclear to what extent the portally drained mesenteric fat depot influences this susceptibility.

Research design and methods: Young high-fat-fed and old obese rats were subjected to 0, 2, 4, or 6 weeks of caloric restriction. Insulin sensitivity (S(I)) was assessed by hyperinsulinemic clamp and lean body mass (LBM) and total body fat were assessed by (18)O-water administration.

Results: Six weeks of caloric restriction caused a similar reduction in body weight in young and old animals (P = 0.748) that was not due to reduced subcutaneous fat or LBM, but rather preferential loss of abdominal fat (P < 0.05). Most notably, mesenteric fat was reduced equivalently in young and old rats after 6 weeks of caloric restriction ( approximately decrease 53%; P = 0.537). Despite similar visceral fat loss, S(I) improved less in old ( increase 32.76 +/- 9.80%) than in young ( increase 82.91 +/- 12.66%) rats versus week 0. In addition, there was significantly more reversal of fat accumulation in the liver in young (% reduction: 89 +/- 2) versus old (64 +/- 5) rats (P < 0.0001). Furthermore, in young rats, S(I) changed much more rapidly for a given change in mesenteric fat versus other abdominal depots (slope = 0.53 vs. < or =0.27 kg/min/mg per % fat). CONCLUSIONS Improved S(I) during caloric restriction correlated with a preferential abdominal fat loss. This improvement was refractory in older animals, likely because of slower liberation of hepatic lipid. Furthermore, mesenteric fat was a better predictor of S(I) than other abdominal depots in young but not old rats. These results suggest a singular role for mesenteric fat to determine insulin resistance. This role may be related to delivery of lipid to liver, and associated accumulation of liver fat.

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Dependency of insulin sensitivity on abdominal fat depot size. The correlation among epididymal (A), perirenal (B), and mesenteric fat (C) normalized to body weight vs. insulin resistance (1/whole-body SI) in all young and old rats used in the study. Correlations are determined for all young and all old rats using the general linear model. A significant difference between young and old slopes was only found for the mesenteric fat depot, and thus visceral fat. Y, young; O, old; m, slope.
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Figure 4: Dependency of insulin sensitivity on abdominal fat depot size. The correlation among epididymal (A), perirenal (B), and mesenteric fat (C) normalized to body weight vs. insulin resistance (1/whole-body SI) in all young and old rats used in the study. Correlations are determined for all young and all old rats using the general linear model. A significant difference between young and old slopes was only found for the mesenteric fat depot, and thus visceral fat. Y, young; O, old; m, slope.

Mentions: To determine the dependency of SI on abdominal adiposity, we performed multiple linear regression analysis to correlate changes in abdominal fat pads versus whole-body insulin resistance (1/SI; Fig. 4). Abdominal fat correlated positively with insulin resistance for young and old rats (P < 0.001). The impact of fat depots classically called visceral fat, epididymal and perirenal fat was not different for young and old rats (effect of age epididymal fat: P = 0.227, perirenal fat: P = 0.100). In addition, there was no age × fat interaction for either depot (epididymal fat: P = 0.499, perirenal fat: 0.139). In striking contrast, true visceral fat loss, as measured by the mesenteric depot, exerted a much stronger effect on insulin sensitivity in young versus old rats (slope: young: 0.053, old: 0.17 kg/min/mg per % fat; effect of age: P = 0.001; age × fat interaction: P < 0.001). Moreover, mesenteric fat appeared to play a far greater role in determining SI than did other depots in young rats as evidenced by more than a doubling of slope, whereas this increased dependence was not observed with old rats (slope = 0.17). These data suggest not only a stronger effect of true (i.e., mesenteric) visceral fat in insulin resistance versus other abdominal depots, but also a sharply reduced interaction in older animals.


Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats.

Catalano KJ, Stefanovski D, Bergman RN - Diabetes (2010)

Dependency of insulin sensitivity on abdominal fat depot size. The correlation among epididymal (A), perirenal (B), and mesenteric fat (C) normalized to body weight vs. insulin resistance (1/whole-body SI) in all young and old rats used in the study. Correlations are determined for all young and all old rats using the general linear model. A significant difference between young and old slopes was only found for the mesenteric fat depot, and thus visceral fat. Y, young; O, old; m, slope.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874702&req=5

Figure 4: Dependency of insulin sensitivity on abdominal fat depot size. The correlation among epididymal (A), perirenal (B), and mesenteric fat (C) normalized to body weight vs. insulin resistance (1/whole-body SI) in all young and old rats used in the study. Correlations are determined for all young and all old rats using the general linear model. A significant difference between young and old slopes was only found for the mesenteric fat depot, and thus visceral fat. Y, young; O, old; m, slope.
Mentions: To determine the dependency of SI on abdominal adiposity, we performed multiple linear regression analysis to correlate changes in abdominal fat pads versus whole-body insulin resistance (1/SI; Fig. 4). Abdominal fat correlated positively with insulin resistance for young and old rats (P < 0.001). The impact of fat depots classically called visceral fat, epididymal and perirenal fat was not different for young and old rats (effect of age epididymal fat: P = 0.227, perirenal fat: P = 0.100). In addition, there was no age × fat interaction for either depot (epididymal fat: P = 0.499, perirenal fat: 0.139). In striking contrast, true visceral fat loss, as measured by the mesenteric depot, exerted a much stronger effect on insulin sensitivity in young versus old rats (slope: young: 0.053, old: 0.17 kg/min/mg per % fat; effect of age: P = 0.001; age × fat interaction: P < 0.001). Moreover, mesenteric fat appeared to play a far greater role in determining SI than did other depots in young rats as evidenced by more than a doubling of slope, whereas this increased dependence was not observed with old rats (slope = 0.17). These data suggest not only a stronger effect of true (i.e., mesenteric) visceral fat in insulin resistance versus other abdominal depots, but also a sharply reduced interaction in older animals.

Bottom Line: In addition, there was significantly more reversal of fat accumulation in the liver in young (% reduction: 89 +/- 2) versus old (64 +/- 5) rats (P < 0.0001).These results suggest a singular role for mesenteric fat to determine insulin resistance.This role may be related to delivery of lipid to liver, and associated accumulation of liver fat.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.

ABSTRACT

Objective: Age-associated insulin resistance may be caused by increased visceral adiposity and older animals appear to be more susceptible to obesity-related resistance than young animals. However, it is unclear to what extent the portally drained mesenteric fat depot influences this susceptibility.

Research design and methods: Young high-fat-fed and old obese rats were subjected to 0, 2, 4, or 6 weeks of caloric restriction. Insulin sensitivity (S(I)) was assessed by hyperinsulinemic clamp and lean body mass (LBM) and total body fat were assessed by (18)O-water administration.

Results: Six weeks of caloric restriction caused a similar reduction in body weight in young and old animals (P = 0.748) that was not due to reduced subcutaneous fat or LBM, but rather preferential loss of abdominal fat (P < 0.05). Most notably, mesenteric fat was reduced equivalently in young and old rats after 6 weeks of caloric restriction ( approximately decrease 53%; P = 0.537). Despite similar visceral fat loss, S(I) improved less in old ( increase 32.76 +/- 9.80%) than in young ( increase 82.91 +/- 12.66%) rats versus week 0. In addition, there was significantly more reversal of fat accumulation in the liver in young (% reduction: 89 +/- 2) versus old (64 +/- 5) rats (P < 0.0001). Furthermore, in young rats, S(I) changed much more rapidly for a given change in mesenteric fat versus other abdominal depots (slope = 0.53 vs. < or =0.27 kg/min/mg per % fat). CONCLUSIONS Improved S(I) during caloric restriction correlated with a preferential abdominal fat loss. This improvement was refractory in older animals, likely because of slower liberation of hepatic lipid. Furthermore, mesenteric fat was a better predictor of S(I) than other abdominal depots in young but not old rats. These results suggest a singular role for mesenteric fat to determine insulin resistance. This role may be related to delivery of lipid to liver, and associated accumulation of liver fat.

Show MeSH
Related in: MedlinePlus