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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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Circulating adipokine and liver triglyceride content. Plasma levels of adiponectin (A), resistin (B), leptin (C), and lipid content (D) in liver in young and old rats exposed to 0, 2, 4, or 6 weeks of caloric restriction. Data are means ± SEMs. Statistical significance was determined using two-way ANOVAs for the effect of time and age with post hoc Tukey tests for individual comparisons. *P < 0.05 for young vs. week 0 and old vs. week 0; §P < 0.05 young vs. old.
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Figure 5: Circulating adipokine and liver triglyceride content. Plasma levels of adiponectin (A), resistin (B), leptin (C), and lipid content (D) in liver in young and old rats exposed to 0, 2, 4, or 6 weeks of caloric restriction. Data are means ± SEMs. Statistical significance was determined using two-way ANOVAs for the effect of time and age with post hoc Tukey tests for individual comparisons. *P < 0.05 for young vs. week 0 and old vs. week 0; §P < 0.05 young vs. old.

Mentions: To determine potential mechanisms of this differential relationship, we measured several circulating adipokines: adiponectin, resistin, and leptin (Fig. 5A–C). Changes in neither adiponectin nor resistin appeared to be responsible for the differential response to caloric restriction in old rats. As might be expected, leptin levels followed the changes in absolute adiposity observed in both obese groups, and the persistently high levels after 6 weeks of caloric restriction in old rats are likely due to an appreciable degree of remaining adiposity in these 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)

Circulating adipokine and liver triglyceride content. Plasma levels of adiponectin (A), resistin (B), leptin (C), and lipid content (D) in liver in young and old rats exposed to 0, 2, 4, or 6 weeks of caloric restriction. Data are means ± SEMs. Statistical significance was determined using two-way ANOVAs for the effect of time and age with post hoc Tukey tests for individual comparisons. *P < 0.05 for young vs. week 0 and old vs. week 0; §P < 0.05 young vs. old.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Circulating adipokine and liver triglyceride content. Plasma levels of adiponectin (A), resistin (B), leptin (C), and lipid content (D) in liver in young and old rats exposed to 0, 2, 4, or 6 weeks of caloric restriction. Data are means ± SEMs. Statistical significance was determined using two-way ANOVAs for the effect of time and age with post hoc Tukey tests for individual comparisons. *P < 0.05 for young vs. week 0 and old vs. week 0; §P < 0.05 young vs. old.
Mentions: To determine potential mechanisms of this differential relationship, we measured several circulating adipokines: adiponectin, resistin, and leptin (Fig. 5A–C). Changes in neither adiponectin nor resistin appeared to be responsible for the differential response to caloric restriction in old rats. As might be expected, leptin levels followed the changes in absolute adiposity observed in both obese groups, and the persistently high levels after 6 weeks of caloric restriction in old rats are likely due to an appreciable degree of remaining adiposity in these 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