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High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets.

ABSTRACT: The administration of estradiol-17? (E) to animal models after loss of ovarian steroid production has many beneficial effects on neural functions, particularly in the serotonin system in nonhuman primates (NHPs). E also has anorexic effects, although the mechanism of action is not well defined. In the US, obesity has reached epidemic proportions, and blame is partially directed at the Western style diet, which is high in fat and sugar. This study examined the interaction of E and diet in surgically menopausal nonhuman primates with a 2×2 block design. Marmosets (Callithrix jacchus; n=4/group) were placed on control-low fat diet (LFD; 14%kcal from fat) or high fat diet (HFD; 28%kcal from fat) 1month prior to ovariectomy (Ovx). Empty (placebo) or E-filled Silastic capsules were implanted immediately following Ovx surgery. Treatments extended 6months. The established groups were: placebo+LFD, E+LFD, placebo+HFD, or E+HFD. At necropsy, the brain was flushed with saline and harvested. The midbrain was dissected and a small block containing the dorsal raphe nucleus was processed for qRT-PCR using Evagreen (Biotinum). Genes previously found to impact serotonin neural functions were examined. Results were compared with 2-way ANOVA followed by Bonferroni post-hoc tests or Cohen's D analysis. There was a significant effect of treatment on tryptophan hydroxylase 2 (TPH2) across the groups (p=0.019). E stimulated TPH2 expression and HFD prevented E-stimulated TPH2 expression (p<0.01). Treatment differentially affected monoamine oxidase B (MAO-B) across the groups (p=0.05). E increased MAO-B with LFD, and this stimulatory effect was prevented by HFD (p<0.05). There was a significant difference between treatments in corticotrophin releasing factor-receptor 2 (CRF-R2) expression (p=0.012). E increased CRF-R2 and this stimulatory effect was blocked by HFD (p<0.01). Regardless of diet, E increased Fev mRNA (p=0.028) and decreased CRF-receptor 1 (CRF-R1) mRNA (p=0.04). HFD suppressed urocortin 1 (UCN1; stresscopin) expression (p=0.045) but E treatment had no effect. Monoamine oxidase A (MAO-A) was different due to treatment across the groups (p=0.028). MAO-A was increased in the E+HFD group (p<0.01) whereas previous studies showed E suppressed MAO-A in macaques. The serotonin reuptake transporter (SERT), the serotonin 1A receptor (5HT1A), estrogen receptor beta (ER?) and progestin receptor (PR) expressions were not different between groups. Estrogen receptor alpha (ER?) was undetectable. In summary, the data indicate that important actions of hormone therapy in the serotonin system may be lost in the context of a HFD.

SUBMITTER: Bethea CL

PROVIDER: S-EPMC4339406 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets.

Bethea Cynthia L CL Reddy Arubala P AP Flowers Matthew M Shapiro Robert A RA Colman Ricki J RJ Abbott David H DH Levine Jon E JE

Progress in neuro-psychopharmacology & biological psychiatry 20141224

The administration of estradiol-17β (E) to animal models after loss of ovarian steroid production has many beneficial effects on neural functions, particularly in the serotonin system in nonhuman primates (NHPs). E also has anorexic effects, although the mechanism of action is not well defined. In the US, obesity has reached epidemic proportions, and blame is partially directed at the Western style diet, which is high in fat and sugar. This study examined the interaction of E and diet in surgica ...[more]

PMID: 25542371

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Project description:High-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma β-hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver. Adult male Wistar rats were fed diets with varying amounts of protein, carbohydrates and fat for 5 weeks. At the end of the experiment, rats were killed and tanscriptome analysis was performed on pooled liver samples.

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High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets.

Publications

High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets.

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