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Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women.

ABSTRACT: Adipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000?IU/day oral vitamin D3 supplementation (N?=?39) vs. placebo (N?=?40) on the expression of 5 genes in breast and adipose tissue in overweight/obese postmenopausal women (50-75 years). All participants had serum 25-hydroxyvitamin D (25(OH)D) levels???10-<32?ng/mL ("insufficient") and concurrently completed a behavioral weight loss program. Random periareolar fine needle aspiration (RPFNA) and abdominal subcutaneous adipose tissue biopsies were performed at baseline and 12 months. Changes in expression of aromatase (CYP19A1), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), monocyte-chemoattractant protein 1 (MCP-1), and vitamin D receptor (VDR) were analyzed by qRT-PCR. Compared to placebo, 2000?IU vitamin D did not show significant effects on gene expression in breast or adipose tissue. Replete women (i.e., 25(OH)D???32?ng/mL; N?=?17) showed a small decrease in MCP-1 expression compared to an increase among women who remained 'insufficient' despite supplementation (N?=?12) (Replete:-1.6% vs. Non-replete: 61.2%, p?=?0.015) in breast, but not adipose tissue. No statistically significant differences in gene expression were detected according to degree of weight loss. Vitamin D repletion during weight loss may have different effects on gene expression in breast and adipose tissue. Further research on the localized effects of vitamin D is needed to determine its effect on breast cancer risk.

SUBMITTER: Mason C

PROVIDER: S-EPMC5460115 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women.

Mason Caitlin C Wang Lei L Duggan Catherine C Imayama Ikuyo I Thomas Sushma S SS Wang Ching-Yun CY Korde Larissa A LA McTiernan Anne A

NPJ breast cancer 20170421

Adipose tissue is involved in the etiology of postmenopausal breast cancer, possibly through increased sex steroid hormone production, inflammation, and altered adipokines. Vitamin D may affect these pathways but its effect on gene expression in different tissues has not been examined. Within a double-blind, 12-month placebo-controlled randomized trial, we compared 2000 IU/day oral vitamin D3 supplementation (N = 39) vs. placebo (N = 40) on the expression of 5 genes in b ...[more]

PMID: 28649655

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Project description:The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program.Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32?ng/mL ("insufficient") were randomized to either weight loss + 2,000?IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations.The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P?>?0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend?=?0.01), and larger decreases in free and bioavailable estradiol (Ptrend?=?0.04, Ptrend?=?0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n?=?38), to women who became replete (25-hydroxyvitamin D ?32?ng/mL; n?=?53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7?pg/mL), free testosterone (-0.8 vs -0.3?pg/mL), and bioavailable testosterone (-1.8 vs -0.6?ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7?nmol/L) (all P?<?0.05), even after adjusting for differences in total 12-month weight loss.Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.

Project description:Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27?±?2 versus C 26?±?2?ng/mL; p?=?0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34?±?9 versus C 26?±?12?ng/g; p?=?0.63) or OM compartments (OB 51?±?13 versus C 30?±?18?ng/g; p?=?0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3?±?0.6 versus 0.4?±?0.8?mg, respectively; p?<?0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research.

Project description:BACKGROUND:Microbiota and bile acids in the gastrointestinal tract profoundly alter systemic metabolic processes. In obese subjects, gradual weight loss ameliorates adipose tissue inflammation and related systemic changes. We assessed how rapid weight loss due to a very low calorie diet (VLCD) affects the fecal microbiome and fecal bile acid composition, and their interactions with the plasma metabolome and subcutaneous adipose tissue inflammation in obesity. METHODS:We performed a prospective cohort study of VLCD-induced weight loss of 10% in ten grades 2-3 obese postmenopausal women in a metabolic unit. Baseline and post weight loss evaluation included fasting plasma analyzed by mass spectrometry, adipose tissue transcription by RNA sequencing, stool 16S rRNA sequencing for fecal microbiota, fecal bile acids by mass spectrometry, and urinary metabolic phenotyping by 1H-NMR spectroscopy. Outcome measures included mixed model correlations between changes in fecal microbiota and bile acid composition with changes in plasma metabolite and adipose tissue gene expression pathways. RESULTS:Alterations in the urinary metabolic phenotype following VLCD-induced weight loss were consistent with starvation ketosis, protein sparing, and disruptions to the functional status of the gut microbiota. We show that the core microbiome was preserved during VLCD-induced weight loss, but with changes in several groups of bacterial taxa with functional implications. UniFrac analysis showed overall parallel shifts in community structure, corresponding to reduced abundance of the genus Roseburia and increased Christensenellaceae;g__ (unknown genus). Imputed microbial functions showed changes in fat and carbohydrate metabolism. A significant fall in fecal total bile acid concentration and reduced deconjugation and 7-?-dihydroxylation were accompanied by significant changes in several bacterial taxa. Individual bile acids in feces correlated with amino acid, purine, and lipid metabolic pathways in plasma. Furthermore, several fecal bile acids and bacterial species correlated with altered gene expression pathways in adipose tissue. CONCLUSIONS:VLCD dietary intervention in obese women changed the composition of several fecal microbial populations while preserving the core fecal microbiome. Changes in individual microbial taxa and their functions correlated with variations in the plasma metabolome, fecal bile acid composition, and adipose tissue transcriptome. Trial Registration ClinicalTrials.gov NCT01699906, 4-Oct-2012, Retrospectively registered. URL- https://clinicaltrials.gov/ct2/show/NCT01699906.

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Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women.

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Gene expression in breast and adipose tissue after 12 months of weight loss and vitamin D supplementation in postmenopausal women.

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