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Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.

ABSTRACT: Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment. In addition, CFD reduced the hepatic p-Akt/Akt ratio in response to acute insulin administration. Moreover, CFD increased serum triglyceride levels, upregulated hepatic Acc1 and Fasn mRNA expression, and downregulated hepatic Cd36 and ApoB mRNA expression. After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance. This study demonstrates that folate deficiency could induce obesity, glucose and lipid metabolism disorders and subsequent cognitive dysfunction.

SUBMITTER: Zhao M

PROVIDER: S-EPMC6112663 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.

Zhao Mei M Yuan Man Man MM Yuan Li L Huang Li Li LL Liao Jian Hong JH Yu Xiao Ling XL Su Chang C Chen Yuan Hua YH Yang Yu Ying YY Yu Huan H Xu De Xiang X

PloS one 20180828 8

Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum f ...[more]

PMID: 30153273

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Project description:Imbalanced dietary habits are closely associated with poor micronutrients status and the development of obesity. Previous studies have shown that serum folate level is decreased in obese individuals. However, whether folate deficiency could result in adiposity is still unclear. The aim of this study was to investigate the effects of dietary folate on lipid accumulation and leptin production using both in vivo and in vitro studies. Male C57BL/6 mice were fed with a diet with (f1) or without (f0) folate in a high-fat (HF) diet containing high-sucrose (HFS-f1, HFS-f0) for 4.5-5 months in Experiment 1, or an HF diet (HF-f1, HF-f0) for 12 months in Experiment 2, or an HF diet containing high-fructose (HFF-f1, HFF-f0) for 12 months in Experiment 3, compared with the normal-fat (NF-f1, NF-f0) diet, respectively. The serum levels of folate and leptin, white adipose tissue (WAT), size of adipocytes, hepatic contents of triglyceride (TG), and cholesterol were measured. In vitro study, TG contents, proinflammatory cytokines, leptin, and expressions of hypoxia-inducible factor (HIF)-1α and lipogenesis-related genes of 3T3-L1 adipocytes cultured with (f1) or without (f0) folate were assayed. The results showed that folate deficiency together with a high-fat diet (HFS-f0, HF-f0, HFF-f0) had higher WAT mass, adipocyte size, serum leptin level, and hepatic TG compared to those of the folate-sufficient groups (HFS-f1, HF-f1, and HFF-f1). Folate deficiency with a high-fat high -sucrose or -fructose diet (HFS-f0, HFF-f0) significantly increased the body weight of the mice. Increased intracellular TG, leptin, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6 levels, and the expression of Hif1α and lipogenesis-related genes Cebpα, Cebpβ, Acc1, Fasn, and Fabp4 were also detected in folate-deficient 3T3-L1 adipocytes. Our results suggested that folate deficiency increased lipid accumulation and leptin production of adipocytes, and thus, inadequate folate status might be one of the risk factors for adiposity.

Dataset Information

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.

Publications

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.

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