Department of Physiology and Biophysics, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.
Diabetes. 2010 Jun;59(6):1416-23. doi: 10.2337/db08-0675. Epub 2010 Mar 18.
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 (S(I)) was assessed by hyperinsulinemic clamp and lean body mass (LBM) and total body fat were assessed by (18)O-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 ( 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.
与年龄相关的胰岛素抵抗可能是由于内脏脂肪增加引起的，而且与年轻动物相比，老年动物似乎更容易受到肥胖相关的抵抗。然而，肠系膜脂肪库对这种易感性的影响程度尚不清楚。
年轻高脂喂养的肥胖大鼠和老年肥胖大鼠分别接受 0、2、4 或 6 周的热量限制。通过高胰岛素-正葡萄糖钳夹法评估胰岛素敏感性（S（I）），通过（18）O-水给药评估瘦体重（LBM）和全身脂肪量。
6 周的热量限制使年轻和老年动物的体重减轻相似（P = 0.748），这不是由于皮下脂肪或 LBM 的减少，而是由于腹部脂肪的优先减少（P < 0.05）。值得注意的是，6 周热量限制后，肠系膜脂肪在年轻和老年大鼠中减少的程度相同（约减少 53%；P = 0.537）。尽管内脏脂肪减少程度相似，但与第 0 周相比，老年大鼠的 S（I）改善较少（增加 32.76 +/- 9.80%），而年轻大鼠则增加较多（增加 82.91 +/- 12.66%）。此外，与老年大鼠（减少 64 +/- 5%）相比，年轻大鼠的肝脏脂肪积累逆转更为明显（减少 89 +/- 2%）（P < 0.0001）。此外，在年轻大鼠中，S（I）的变化与肠系膜脂肪相对于其他腹部脂肪库的变化更为迅速（斜率=0.53 与 <或=0.27 kg/min/mg/脂肪%）。
热量限制期间 S（I）的改善与腹部脂肪的优先减少有关。这种改善在老年动物中是抵抗的，可能是由于肝脏脂质的释放较慢。此外，肠系膜脂肪在年轻大鼠中比其他腹部脂肪库更能预测 S（I），但在老年大鼠中则不然。这些结果表明肠系膜脂肪在决定胰岛素抵抗方面起着独特的作用。这种作用可能与肝脏脂质的输送以及相关的肝脏脂肪积累有关。
