Gene expression profile at single cell level of lungs of adult male and female C57BL/6 mice with andwithout high-fat diet-induced obesity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE279918 | GEO | 2024/12/31
REPOSITORIES: GEO
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Project description:Since there are limited studies analyzing the impact of age, sex and obesity on cutaneous repair, the current study evaluated excisional skin wound healing as a function of age, sex and diet in C57BL/6 mice subjected to either low (LFD) or high (HFD) fat diet. Older mice accumulated increased body fat relative to younger mice under HFD. Skin wound healing at particular stages was affected by age in the aspect of Tgfβ-1, MCP-1, Mmp-9 and Mmp-13 expression. The most profound, cumulative effect was observed for the combination of two parameters: age and sex. While skin of younger males displayed extremely high collagen 1 and collagen 3 expression, younger females showed exceptionally high Mmp-13 expression at day 3 and 7 after injury. Diet as a single variable modified the thickness of dermis due to increased dermal White Adipose Tissue (dWAT) accumulation in mice fed HFD. The combination of age and diet affected the re-epithelialization and inflammatory response of injured skin. Overall, our data indicate that age has the most fundamental impact although all components (age, sex and diet) contribute to skin repair.
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Project description:Background/objectivesRecent findings have highlighted the detrimental influence of maternal overnutrition and obesity on fetal development and early life development. However, there are no evidence-based guidelines regarding the optimal strategy for dietary intervention before pregnancy.Subjects/methodsWe used a murine model to study whether switching from a high-fat (HF) diet to a normal-fat (NF) diet (H1N group) 1 week before pregnancy could lead to in utero reprogramming of female offspring obesity; comparator groups were offspring given a consistent maternal HF group or NF group until weaning. After weaning, all female offspring were given the HF diet for either 9 or 12 weeks before being killed humanely.ResultsH1N treatment did not result in maternal weight loss before pregnancy. NF offsprings were neither obese nor glucose intolerant during the entire experimental period. H1N offsprings were most obese after the 12-week postweaning HF diet and displayed glucose intolerance earlier than HF offsprings. Our mechanistic study showed reduced adipocyte insulin receptor substrate 1 (IRS1) and hepatic IRS2 expression and increased adipocyte p-Ser(636/639) and p-Ser(612) of H1N or HF offspring compared with that in the NF offspring. Among all groups, the H1N offspring had lowest level of IRS1 and the highest levels of p-Ser(636/639) and p-Ser(612) in gonadal adipocyte. In addition, the H1N offspring further reduced the expression of Glut4 and Glut2, vs those of the HF offspring, which was lower compared with the NF offspring. There were also enhanced expression of genes inhibiting glycogenesis and decreased hepatic glycogen in H1N vs HF or NF offspring. Furthermore, we showed extremely higher expression of lipogenesis and adipogenesis genes in gonadal adipocytes of H1N offspring compared with all other groups.ConclusionsOur results suggest that a transition from an HF diet to an NF diet shortly before pregnancy, without resulting in maternal weight loss, is not necessarily beneficial and may have deleterious effects on offspring.
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