Early life malnutrition and risk of T2DM adulthood: evidence from the lower socioeconomic status of northwest Chinese population

ObjectiveThis study aimed to explore whether famine exposure during early life are associated with a high risk of Type 2 Diabetes Mellitus (T2DM) in adulthood and the role of socioeconomic status (SES) on this effect.Materials and methodsWe conducted a secondary data analysis based on data from a cross-sectional survey, collected 3,355 participants born between January 1, 1941 and December 31, 1966. Participants were categorized into four groups based on their date of birth, unexposed (individuals born in 1963–1966), infant exposed (individuals born in 1959–1962), childhood exposed (individuals born in 1949–1958), and adolescent exposed (born in 1941–1948). The association of famine exposure with T2DM risk in adults and conducted separately in plain area and mountain area was assessed using logistics regression model.Result22.35% of participants were diagnosed with T2DM, of which 43.47% were from the childhood famine-exposed group, representing the highest proportion among all subgroups (p < 0.001). Participants exposed to famine during childhood and adolescence from the lower SES mountain areas showed a significantly higher prevalence of T2DM in adulthood than those from the plain areas (p < 0.001). The adolescence stage exposed famine will increase the risk of T2DM in the mountain area (OR 2.46, 95% CI 1.61, 3.77).ConclusionNo strong evidence demonstrates that exposure to famine during the early life stage increases the risk of developing T2DM in adulthood. However, populations with lower SES are likely to be exposed to more risk factors for T2DM

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Wind Pressure Coefficients Zoning Method Based on an Unsupervised Learning Algorithm

Damage of the cladding structures usually occurs from the wind-sensitive part, which can cause the damaged conditions to obviously vary from different areas especially on a large roof surface. It is necessary to design optimization due to the difference of wind loads by defining more accurate wind pressure coefficient (WPC) zones according to the wind vulnerability analysis. The existing wind pressure coefficient zoning methods (WPCZM) have successfully been used to characterize the simple roof shapes. But the solutions for the complex and irregular roof shapes generally rely on the empirical judgment which is defective to the wind loading analysis. In this study, a classification concept for WPC values on the roof surface is presented based on the unsupervised learning algorithm, which is not limited by the roof geometry and can realize the multitype WPC zoning more accurately. As a typical unsupervised learning algorithm, an improved K-means clustering is proposed to develop a new WPCZM to verify the above concept. And a method to determine the optimal K-value is presented by using the K-means clustering test and clustering validity indices to overcome the difficulty of obtaining the cluster number in the traditional methods. As an example, the most unfavorable pressure and suction WPC zones are studied on a flat roof structure with single wind direction and full wind direction based on the data obtained from the wind tunnel test. As another example, the mean pressure coefficient zones are studied on a saddle roof structure under 0- and 45-degree wind direction based on the data obtained by the wind tunnel test. And the proposed WPCZM is illustrated and verified

Ameliorating effects of Sporidiobolus pararoseus extract on dyslipidemia in mice with high-fat diet-induced obesity

The study aims to elucidate the intervention effect of Sporidiobolus pararoseus (S. p.) extract on the lipid metabolism in Kunming mice with high-fat diet-induced obesity with Max EPA as a control. Ten mice were randomly selected from 60 mice as control group and the remaining 50 mice were fed with a high-fat diet to establish a dyslipidemia model. After 4 weeks, these 50 mice were randomly divided into 5 groups: high-fat model group, Max EPA group, and the 3 groups of different doses of S. p. extract (LD, MD and HD). After eight weeks, the mice were sacrificed and related parameters were measured. Compared with the high-fat group, S. p. extract (HD) group showed the significantly decreased body weight and serum TC, TG and LDL-c levels as well as the increased HDL-c level. RT-PCR results showed that the mRNA expression of SREBP-1c, FAS and ACC in S. p. extract supplementation group was lower than those in high-fat diet group whereas the expression of CPT-1 in S. p. extract supplementation group was higher than that of the high-fat diet group. Our results implied that the intake of S. p. extract might benefit the patients with dyslipidemia. Therefore, S. p. extract may be developed as a dietary supplement for ameliorating lipid metabolism of obese people.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

α-Ketoglutarate prevents hyperlipidemia-induced fatty liver mitochondrial dysfunction and oxidative stress by activating the AMPK-pgc-1α/Nrf2 pathway

α-Ketoglutarate (AKG), a crucial intermediate in the tricarboxylic acid cycle, has been demonstrated to mitigate hyperlipidemia-induced dyslipidemia and endothelial damage. While hyperlipidemia stands as a major trigger for non-alcoholic fatty liver disease, the protection of AKG on hyperlipidemia-induced hepatic metabolic disorders remains underexplored. This study aims to investigate the potential protective effects and mechanisms of AKG against hepatic lipid metabolic disorders caused by acute hyperlipidemia. Our observations indicate that AKG effectively alleviates hepatic lipid accumulation, mitochondrial dysfunction, and loss of redox homeostasis in P407-induced hyperlipidemia mice, as well as in palmitate-injured HepG2 cells and primary hepatocytes. Mechanistic insights reveal that the preventive effects are mediated by activating the AMPK-PGC-1α/Nrf2 pathway. In conclusion, our findings shed light on the role and mechanism of AKG in ameliorating abnormal lipid metabolic disorders in hyperlipidemia-induced fatty liver, suggesting that AKG, an endogenous mitochondrial nutrient, holds promising potential for addressing hyperlipidemia-induced fatty liver conditions

Myxobacteria restrain Phytophthora invasion by scavenging thiamine in soybean rhizosphere via outer membrane vesicle-secreted thiaminase I

Abstract Public metabolites such as vitamins play critical roles in maintaining the ecological functions of microbial community. However, the biochemical and physiological bases for fine-tuning of public metabolites in the microbiome remain poorly understood. Here, we examine the interactions between myxobacteria and Phytophthora sojae, an oomycete pathogen of soybean. We find that host plant and soil microbes complement P. sojae’s auxotrophy for thiamine. Whereas, myxobacteria inhibits Phytophthora growth by a thiaminase I CcThi1 secreted into extracellular environment via outer membrane vesicles (OMVs). CcThi1 scavenges the required thiamine and thus arrests the thiamine sharing behavior of P. sojae from the supplier, which interferes with amino acid metabolism and expression of pathogenic effectors, probably leading to impairment of P. sojae growth and pathogenicity. Moreover, myxobacteria and CcThi1 are highly effective in regulating the thiamine levels in soil, which is correlated with the incidence of soybean Phytophthora root rot. Our findings unravel a novel ecological tactic employed by myxobacteria to maintain the interspecific equilibrium in soil microbial community