integrative-transcriptomic-analysis-obesity-associated-candidate

Integrative Transcriptomic Analysis of Obesity-Associated Candidate Genes in Pediatric Adipose Tissue

Tryptophan metabolism has been linked to pediatric obesity, although the transcriptomic evidence connecting obesity-associated genes with this pathway ...

Nanjing Medical University

Early life nutrition is important in the regulation of metabolism in adulthood. We studied the effects of different fatty acid composition diets on adiposity measures, glucose tolerance, and peripheral glucocorticoid (GC) metabolism in overfed neonatal rats. Rat litters were adjusted to a litter size of three (small litters (SLs)) or ten (normal litters (NLs)) on postnatal day 3 to induce overfeeding or normal feeding respectively. After weaning, SL and NL rats were fed a ω6 polyunsaturated fatty acid (PUFA) diet (14% calories as fat, soybean oil) or high-saturated fatty acid (high-fat; 31% calories as fat, lard) diet until postnatal week 16 respectively. SL rats were also divided into the third group fed a ω3 PUFA diet (14% calories as fat, fish oil). A high-fat diet induced earlier and/or more pronounced weight gain, hyperphagia, glucose intolerance, and hyperlipidemia in SL rats compared with NL rats. In addition, a high-fat diet increased 11β-hsd1 (Hsd11b1) mRNA expression and activity in the retroperitoneal adipose tissue of both litter groups compared with standard chow counterparts, whereas high-fat feeding increased hepatic 11β-hsd1 mRNA expression and activity only in SL rats. SL and a high-fat diet exhibited significant interactions in both retroperitoneal adipose tissue and hepatic 11β-HSD1 activity. Dietary ω3 PUFA offered protection against glucose intolerance and elevated GC exposure in the retroperitoneal adipose tissue and liver of SL rats. Taken together, the results suggest that dietary fatty acid composition in the post-sucking period may interact with neonatal feeding and codetermine metabolic alterations in adulthood.

The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can ω3 polyunsaturated fatty acids prevent adverse programming outcomes?

Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis.

Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats.

Adult diffuse gliomas with FGFR3-TACC3 (F3T3) fusion are rare and highly heterogeneous central nervous system (CNS) tumors. Current research on the biological behavior of these tumors is limited, especially regarding whether histopathologically low-grade tumors are indolent or represent early-stage high-grade tumors, thereby posing challenges for grading. In this single-center study of 17 patients with adult F3T3 fusion diffuse gliomas (F3T3 gliomas), both low- and high-grade F3T3 gliomas presented distinctive recurrent histopathological features, such as oligodendrocyte-like cells, branched vessels and frequent calcifications. Molecularly, TERT promoter mutations and 7+/10- chromosomal alterations were common; one patient with recurrent glioma with histopathological features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) had additional CDK4 and MDM2 amplifications. Methylation profiling of 3 samples revealed varied results. A patient whose tumor had histopathological features consistent with PLNTY and a methylation subtype classified as the mesenchymal subtype of glioblastoma (GBM) experienced tumor recurrence 8 months after surgery. After 5-62 months of follow-up, seven patients relapsed, and six died; the primary tumors of the three patients with recurrence presented histopathological characteristics of low-grade glioma (LGG). GBM patients had worse overall survival than LGG patients (p = 0.035) but similar progression-free survival (p = 0.47), indicating that LGG patients may experience recurrence. For adults with tumors with histopathological features of PLNTY, further molecular and methylation analyses are needed for grading. If TERT promoter mutations are present, even with a PLNTY methylation profile, these tumors can still exhibit the biological behavior of high-grade gliomas.

Article	Year
The effects of dietary fatty acid composition in the post-sucking period on metabolic alterations in adulthood: can ω3 polyunsaturated fatty acids prevent adverse programming outcomes? The Journal of endocrinology\| PubMed ID: 22847675	2012
Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats. The Journal of nutritional biochemistry\| PubMed ID: 25154569	2014
Diffuse glioma with FGFR3-TACC3 fusion in adults is not a homogenous clinicopathological and molecular entity. The journal of pathology. Clinical research\| PubMed ID: 41165398	2025

Chenlin Ji

Biography

JoVE Journal Publications

Other Publications