High-fat diet pre-conditioning improves microvascular remodelling during regeneration of ischaemic mouse skeletal muscle.
- 作者列表："Nwadozi E","Rudnicki M","De Ciantis M","Milkovich S","Pulbere A","Roudier E","Birot O","Gustafsson T","Ellis CG","Haas TL
AIM:Critical limb ischaemia (CLI) is characterized by inadequate angiogenesis, arteriolar remodelling and chronic myopathy, which are most severe in type 2 diabetic patients. Hypertriglyceridaemia, commonly observed in these patients, compromises macrovascular function. However, the effects of high-fat diet-induced increases in circulating lipids on microvascular remodelling are not established. Here, we investigated if high-fat diet would mimic the detrimental effect of type 2 diabetes on post-ischaemia vascular remodelling and muscle regeneration, using a mouse model of hindlimb ischaemia. METHODS:Male C57Bl6/J mice were fed with normal or high-fat diets for 8 weeks prior to unilateral femoral artery ligation. Laser doppler imaging was used to assess limb perfusion recovery. Vascular recovery, inflammation, myofibre regeneration and fibrosis were assessed at 4 or 14 days post-ligation by histology and RNA analyses. Capillary-level haemodynamics were assessed by intravital microscopy of control and regenerating muscles 14 days post-ligation. RESULTS:High-fat diet increased muscle succinate dehydrogenase activity and capillary-level oxygen supply. At 4 days post-ligation, no diet differences were detected in muscle damage, inflammatory infiltration or capillary activation. At 14 days post-ligation, high fat-fed mice displayed accelerated limb blood flow recovery, elevated capillary and arteriole densities as well as greater red blood cell supply rates and capillary-level oxygen supply. Regenerating muscles from high fat-fed mice displayed lower interstitial fat and collagen deposition. CONCLUSION:The muscle-level adaptations to high-fat diet improved multiple aspects of muscle recovery in response to ischaemia and did not recapitulate the worse outcomes seen in diabetic CLI patients.
目的: 重症肢体缺血 (CLI) 以血管生成不足、小动脉重构和慢性肌病为特征，以 2 型糖尿病患者最为严重。在这些患者中常见的高甘油三酯血症损害大血管功能。然而，高脂饮食诱导的循环脂质增加对微血管重塑的影响尚未确定。在这里，我们使用后肢缺血的小鼠模型，研究了高脂饮食是否会模拟 2 型糖尿病对缺血后血管重塑和肌肉再生的有害影响。 方法: 雄性 C57Bl6/J 小鼠在单侧股动脉结扎前给予正常或高脂饮食喂养 8 周。应用激光多普勒成像评估肢体灌注恢复情况。通过组织学和 RNA 分析评估结扎后 4 或 14 天的血管恢复、炎症、肌纤维再生和纤维化。结扎后 14 天，通过活体显微镜观察对照和再生肌评估毛细血管水平的血流动力学。 结果: 高脂饮食增加肌肉琥珀酸脱氢酶活性和毛细血管水平氧供应。结扎后 4 天，未检测到肌肉损伤、炎症浸润或毛细血管激活的饮食差异。结扎后 14 天，高脂喂养的小鼠肢体血流恢复加快，毛细血管和小动脉密度升高，红细胞供应率和毛细血管水平供氧增加。高脂喂养小鼠的再生肌肉显示出较低的间质脂肪和胶原沉积。 结论: 肌肉水平对高脂饮食的适应改善了对缺血的肌肉恢复的多个方面，并没有概括糖尿病 CLI 患者的更差结局。
METHODS:Maintaining adequate daily protein intake is important to maintain muscle mass throughout the lifespan. In this regard, the overnight period has been identified as a window of opportunity to increase protein intake in the elderly. However, it is unknown whether pre-sleep protein intake affects next-morning appetite and, consequently, protein intake. Therefore, the purpose of the current study was to investigate the effects of a pre-sleep protein drink on next-morning appetite, energy intake and metabolism. Twelve older individuals (eight males, four females; age: 71.3 ± 4.2 years) took part in a single-blind randomised cross-over study. After a standardised dinner, participants consumed either a 40-g protein drink, isocaloric maltodextrin drink, or placebo water control before bedtime. Next-morning appetite, energy intake, resting metabolic rate (RMR), respiratory exchange rate (RER), and plasma acylated ghrelin, leptin, glucose, and insulin concentrations were assessed. No between-group differences were observed for appetite and energy intake at breakfast. Furthermore, RMR, RER, and assessed blood markers were not significantly different between any of the treatment groups. Pre-sleep protein intake does not affect next-morning appetite and energy intake and is therefore a viable strategy to increase daily protein intake in an older population.
METHODS:Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30−70 years were retrieved from the Taiwan Biobank Database (2008−2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (β = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.
METHODS:Background For the same BMI, South Asians have a higher body fat percentage, a higher liver fat content and a more adverse metabolic profile than whites. South Asians may have a lower fat oxidation than whites, which could result in an unfavorable metabolic profile when exposed to increased high-fat foods consumption and decreased physical activity as in current modern lifestyle. Objective To determine substrate partitioning, liver fat accumulation and metabolic profile in South Asian and white men in response to overfeeding with high-fat diet under sedentary conditions in a respiration chamber. Design Ten South Asian men (BMI, 18–29 kg/m^2) and 10 white men (BMI, 22–33 kg/m^2), matched for body fat percentage, aged 20–40 year were included. A weight maintenance diet (30% fat, 55% carbohydrate, and 15% protein) was given for 3 days. Thereafter, a baseline measurement of liver fat content (1H-MRS) and blood parameters was performed. Subsequently, subjects were overfed (150% energy requirement) with a high-fat diet (60% fat, 25% carbohydrate, and 15% protein) over 3 consecutive days while staying in a respiration chamber mimicking a sedentary lifestyle. Energy expenditure and substrate use were measured for 3 × 24-h. Liver fat and blood parameters were measured again after the subjects left the chamber. Results The 24-h fat oxidation as a percentage of total energy expenditure did not differ between ethnicities ( P = 0.30). Overfeeding increased liver fat content ( P = 0.02), but the increase did not differ between ethnicities ( P = 0.64). In South Asians, overfeeding tended to increase LDL-cholesterol ( P = 0.08), tended to decrease glucose clearance ( P = 0.06) and tended to elevate insulin response ( P = 0.07) slightly more than whites. Conclusions Despite a similar substrate partitioning and similar accretion of liver fat, overfeeding with high-fat under sedentary conditions tended to have more adverse effects on the lipid profile and insulin sensitivity in South Asians.