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Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.

ABSTRACT: The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V (Scg5; also referred to as Sgne1), as a candidate gene for growth traits.Through a combination of DNA microarray analysis and quantitative PCR we identified a strong expression quantitative trait locus (eQTL) regulating Scg5 expression in two mouse chromosome 2 congenic strains and three additional F2 intercrosses. More importantly, the eQTL was coincident with a body weight QTL in congenic mice and Scg5 expression was negatively correlated with body weight in two of the F2 intercrosses. Analysis of haplotype blocks and genomic sequencing of Scg5 in high (C3H/HeJ, DBA/2J, BALB/cByJ, CAST/EiJ) and low (C57BL/6J) expressing strains revealed mutations unique to C57BL/6J and possibly responsible for the difference in mRNA abundance. To evaluate the functional consequence of Scg5 overexpression we measured the pituitary levels of 7B2 protein and PCSK2 activity and found both to be increased. In spite of this increase, the level of pituitary alpha-MSH, a PCSK2 processing product, was unaltered.Together, these data support a role for Scg5 in the modulation of body weight.

SUBMITTER: Farber CR

PROVIDER: S-EPMC2386500 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.

Farber Charles R CR Chitwood James J Lee Sang-Nam SN Verdugo Ricardo A RA Islas-Trejo Alma A Rincon Gonzalo G Lindberg Iris I Medrano Juan F JF

BMC genetics 20080425

<h4>Background</h4>The identification of novel genes is critical to understanding the molecular basis of body weight. Towards this goal, we have identified secretogranin V (Scg5; also referred to as Sgne1), as a candidate gene for growth traits.<h4>Results</h4>Through a combination of DNA microarray analysis and quantitative PCR we identified a strong expression quantitative trait locus (eQTL) regulating Scg5 expression in two mouse chromosome 2 congenic strains and three additional F2 intercros ...[more]

PMID: 18439298

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Project description:BackgroundDuring pregnancy, healthy maternal body weight and a nutritionally complete diet provide a favorable environment for fetal development. Yet nearly two-thirds of women of reproductive age in the United States (US) are either overweight or obese. The objective of this research was to investigate the relationship between a measure of dietary diversity and body mass index (BMI) in a sample of women enrolled in a US pregnancy cohort.MethodsDietary data was obtained from one 24-hour dietary recall collected during the third trimester of pregnancy (n = 40). Pre-pregnancy BMI was calculated from pre-pregnancy weight and height self-reported by survey at the time of enrollment. Using the Minimum Dietary Diversity for Women (MDD-W) indicator developed by the Food and Agriculture Organization of the United Nations, dietary data was categorized and scored.ResultsOverall, 35% of participants did not achieve minimum dietary diversity (MDD-W ?5). In addition, 45% of participants were obese, 35% were normal weight and 20% were overweight. Women with higher BMI had lower MDD-W scores than women with lower BMI (p < 0.05). The median MDD-W for both normal and overweight women was ?5 indicating that normal and overweight pregnant women tended to consume a diet that was high in micronutrients. Conversely, the median MDD-W for obese women was below 5 meaning these women tended to consume a diet that was low in micronutrient density. The most commonly consumed food group was grain. In addition, 75% of all participants consumed sweetened drinks. Individuals with an MDD-W score ?5, were more likely to have consumed dark green leafy vegetables, vitamin A-rich fruits or vegetables, other vegetables and other fruits than those with MDD-W scores <5.DiscussionIn this study, we show that a food group diversity indicator that has been shown to reflect adequacy of micronutrient intake in populations from less economically developed countries may also be informative in US populations. Furthermore, these results reflect the importance of encouraging all pregnant women with less varied diets to consume more fruits and vegetables.

Dataset Information

Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.

Publications

Overexpression of Scg5 increases enzymatic activity of PCSK2 and is inversely correlated with body weight in congenic mice.

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