Abstract
BackgroundStudies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society.MethodsThe pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes.ResultsAfter dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05).ConclusionsLBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways.
Highlights
Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear
In the early stage of our study, we found that deoxycholic acid and cholic acid levels in the blood of Low birth weight (LBW) mice were significantly lower than those of normal birth weight mice, suggesting that cholic acid metabolism might play a role in adult type 2 diabetes mellitus caused by LBW [7]
The results showed that the values of HOMA-insulin resistance (IR) in the NH and LH groups were significantly higher than that in the NC group (P < 0.05), and the value of Homoeostasis Model Assessment for Insulin Resistance (HOMA-IR) in the LH group was markedly higher than that in the NH group (P < 0.05, Fig. 2G)
Summary
Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. A previous meta-analysis study used 21 previous clinical studies (313,165 clinical samples), and found that LBW individuals have a significantly increased risk of developing type 2 diabetes and IR compared with other birth weights, as well as IR might be the central pathogenesis of these chronic metabolic diseases [5]. In the early stage of our study, we found that deoxycholic acid and cholic acid levels in the blood of LBW mice were significantly lower than those of normal birth weight mice, suggesting that cholic acid metabolism might play a role in adult type 2 diabetes mellitus caused by LBW [7]. The mechanisms inducing IR and the development of diabetes in LBW individuals remain unclear
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
