Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats.
Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats.
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DOI：
10.2337/db08-0675
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发表时间：
2010-06
期刊：
影响因子：
7.7
通讯作者：
Bergman RN
中科院分区：
文献类型：
--
作者：
Catalano KJ;Stefanovski D;Bergman RN
肥胖相关的胰岛素抵抗可能是由内脏肥胖增加引起的，老年动物似乎比年轻动物更容易受到肥胖相关抵抗的影响。然而，目前还不清楚门静脉引流肠系膜脂肪库在多大程度上影响这种易感性。年轻的高脂肪喂养和老年肥胖大鼠进行0，2，4，或6周的热量限制。采用高胰岛素钳夹法测定胰岛素敏感性（SI），采用18 O-水法测定瘦体重（LBM）和总体脂。6周的热量限制导致年轻和老年动物体重相似的减少（P = 0.748），这不是由于皮下脂肪或LBM减少，而是由于腹部脂肪优先减少（P < 0.05）。最值得注意的是，在6周的热量限制后，年轻和老年大鼠的肠系膜脂肪减少相当（P = 0.537）。尽管内脏脂肪减少相似，但与第0周相比，老年大鼠（↑32.76 ± 9.80%）的SI改善程度低于年轻大鼠（↑82.91 ± 12.66%）。此外，年轻大鼠（减少%：89 ± 2）与老年大鼠（64 ± 5）相比，肝脏中脂肪积累的逆转明显更多（P < 0.0001）。此外，在幼龄大鼠中，肠系膜脂肪的给定变化与其他腹部贮库相比，SI的变化更快（斜率= 0.53与≤0.27 kg/min/mg/ %脂肪）。热量限制期间SI改善与腹部脂肪减少相关。这种改善在老年动物中是难治性的，可能是因为肝脏脂质释放较慢。此外，肠系膜脂肪是一个更好的预测SI比其他腹部仓库在年轻，但不是老年大鼠。这些结果表明肠系膜脂肪在决定胰岛素抵抗方面具有独特的作用。这种作用可能与脂质向肝脏的输送以及相关的肝脏脂肪积累有关。
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. Young high-fat–fed and old obese rats were subjected to 0, 2, 4, or 6 weeks of caloric restriction. Insulin sensitivity (SI) was assessed by hyperinsulinemic clamp and lean body mass (LBM) and total body fat were assessed by 18O-water administration. 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 (∼↓53%; P = 0.537). Despite similar visceral fat loss, SI improved less in old (↑32.76 ± 9.80%) than in young (↑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, SI changed much more rapidly for a given change in mesenteric fat versus other abdominal depots (slope = 0.53 vs. ≤0.27 kg/min/mg per % fat). Improved SI 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 SI 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.