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High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra

高脂饮食抑制过氧化物酶体增殖物激活受体并减少黑质多巴胺能神经元

  • 影响因子:4.32
  • DOI:10.3390/ijms21010207
  • 作者列表:"Yu-Chia Kao","Wei-Yen Wei","Kuen-Jer Tsai","Liang-Chao Wang
  • 发表时间:2020-01-24
Abstract

Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.

摘要

尽管一些流行病学和动物研究已经揭示了肥胖和神经退行性疾病之间的相关性,如帕金森病 (PD),但肥胖诱导的 PD 的潜在病理机制仍不清楚。我们的研究旨在评估饮食诱导的肥胖对大脑多巴胺能通路的影响。五个月,从断奶开始,我们给 C57BL/6 小鼠高脂饮食 (HFD),生成肥胖小鼠模型,并研究饮食是否重新编程了中脑多巴胺能系统。酪氨酸羟化酶染色显示,HFD 导致黑质 (SN) 中多巴胺能神经元减少,但纹状体中没有。它还诱导神经炎症,SN 和纹状体星形胶质细胞增生增加。HFD 暴露小鼠 SN 的树突棘密度降低,提示 HFD 延长改变了多巴胺能神经可塑性。三种过氧化物酶体增殖物激活受体 (PPAR) 亚型 (PPAR-& #945;,PPAR-& #946;/& #948;,PPAR-& #947;) 与对照组相比,HFD 小鼠 SN 和腹侧被盖区的水平显著降低。本研究表明,延长的 HFD 诱导神经炎症,抑制 PPAR 水平,引起中脑多巴胺能神经元变性,并导致令人联想到人类 PD 的症状。据我们所知,这是第一项记录 HFD 对多巴胺能神经元 PPARs 影响的研究。

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影响因子:4.51
发表时间:2020-01-24
来源期刊:Nutrients
DOI:10.3390/nu12010090
作者列表:["Stephen Morehen","Benoit Smeuninx","Molly Perkins","Paul Morgan","Leigh Breen"]

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.

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影响因子:4.32
发表时间:2020-01-24
DOI:10.3390/ijms21010123
作者列表:["Tzi-Peng Yang","Hsiao-Mei Chen","Chao-Chin Hu","Li-Yuan Chen","Fen-Fen Shih","Disline Manli Tantoh","Kuan-Jung Lee","Yi-Chia Liaw","Rong-Tzong Tsai","Yung-Po Liaw"]

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.

翻译标题与摘要 下载文献
影响因子:4.82
发表时间:2020-01-01
DOI:10.1038/s41366-019-0368-2
作者列表:["Wulan, Siti N.","Schrauwen-Hinderling, Vera B.","Westerterp, Klaas R.","Plasqui, Guy"]

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.

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