Maternal high-fat diet induces long-term obesity with sex-dependent metabolic programming of adipocyte differentiation, hypertrophy and dysfunction in the offspring.


  • 影响因子:4.95
  • DOI:10.1042/CS20191229
  • 作者列表:"Litzenburger T","Huber EK","Dinger K","Wilke R","Vohlen C","Selle J","Kadah M","Persigehl T","Heneweer C","Dötsch J","Alejandre Alcazar MA
  • 发表时间:2020-04-02

:Maternal obesity determines obesity and metabolic diseases in the offspring. The white adipose tissue (WAT) orchestrates metabolic pathways, and its dysfunction contributes to metabolic disorders in a sex-dependent manner. Here, we tested if sex-differences influence the molecular mechanisms of metabolic programming of WAT in offspring of obese dams. To this end, maternal obesity was induced with high-fat diet and the offspring were studied at an early phase [postnatal day 21 (P21)], a late phase (P70), and finally P120. At the early phase we found a sex-independent increase of WAT in offspring of obese dams using MRI, which was more pronounced in females than males. While the adipocyte size increased in both sexes, the distribution of WAT differed in males and females. As mechanistic hints, we identified an inflammatory response in females and a senescence-associated reduction of the preadipocyte factor DLK in males. At the late phase, the obese body composition persisted in both sexes, with a partial reversal in females. Moreover, female offspring recovered completely from both the adipocyte hypertrophy and the inflammatory response. These findings were linked to a dysregulation of lipolytic, adipogenic and stemness-related markers as well as AMPKα and Akt signaling. Finally, the sex-dependent metabolic programming persisted with sex-specific differences in adipocyte size until P120. In conclusion, we do not only provide new insights in the molecular mechanisms of sex-dependent metabolic programming of WAT dysfunction, but also highlight the sex-dependent development of low-grade and high-grade pathogenic obesity.


: 母亲肥胖决定了后代的肥胖和代谢性疾病。白色脂肪组织 (WAT) 协调代谢途径,其功能障碍以性别依赖的方式导致代谢紊乱。在这里,我们测试了性别差异是否影响肥胖水坝后代 WAT 代谢编程的分子机制。为此,用高脂饮食诱导母体肥胖,并在早期阶段 [出生后第 21 天 (P21)],晚期阶段 (P70) 研究后代,最后是 P120.在早期阶段,我们使用 MRI 发现肥胖水坝后代的 WAT 增加与性别无关,这在女性中比男性更明显。虽然脂肪细胞大小在两种性别中增加,但 WAT 在男性和女性中的分布不同。作为机制提示,我们发现了女性的炎症反应和男性衰老相关的前脂肪细胞因子 DLK 的减少。在晚期阶段,肥胖的身体成分在两性中持续存在,在女性中部分逆转。此外,雌性后代从脂肪细胞肥大和炎症反应中完全恢复。这些发现与脂解、成脂和干性相关标志物以及 ampk α 和 Akt 信号的失调有关。最后,性别依赖性代谢编程持续存在脂肪细胞大小的性别特异性差异,直到 p120。总之,我们不仅在 WAT 功能障碍的性别依赖性代谢编程的分子机制方面提供了新的见解,而且突出了低、高致病性肥胖的性别依赖性发展。



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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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.

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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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