Anterior Pituitary Transcriptomics Following a High-Fat Diet: Impact of Oxidative Stress on Cell Metabolism

Abstract Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress...

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Published in:	Endocrinology (Philadelphia) Vol. 165; no. 2
Main Authors:	Miles, Tiffany K, Odle, Angela K, Byrum, Stephanie D, Lagasse, Alex, Haney, Anessa, Ortega, Victoria G, Bolen, Cole R, Banik, Jewel, Reddick, Milla M, Herdman, Ashley, MacNicol, Melanie C, MacNicol, Angus M, Childs, Gwen V
Format:	Journal Article
Language:	English
Published:	US Oxford University Press 23-12-2023
Subjects:	Adenosine triphosphate Adiponectin Animals ATP Body weight gain Diet Diet, High-Fat - adverse effects Energy expenditure Fat metabolism Female Females Gene expression Gene Expression Profiling Gene sequencing Growth hormones High fat diet High protein diet Hormones Interleukin 6 Leptin Male Males Mice Mice, Inbred C57BL Monocyte chemoattractant protein 1 Monocytes Necrosis Obesity Obesity - metabolism Oxidative Stress Phenotypes Pituitary (anterior) Population studies Prolactin Protein biosynthesis Protein synthesis Protein turnover Proteins Pulse amplitude Quorum sensing Sequence analysis Stem cells Transcriptomes Transcriptomics Weight Gain pituitary sc-RNA-seq high fat diet obesity oxidative stress
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Summary:	Abstract Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial adenosine triphosphate production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress, and adding to their allostatic load. We hypothesized that pituitary function is vulnerable to the stress of obesity. Here, we utilized a 10- to 15-week high-fat diet (HFD, 60%) in a thermoneutral environment to promote obesity, testing both male and female FVB.129P mice. We quantified serum hormones and cytokines, characterized the metabolic phenotype, and defined changes in the pituitary transcriptome using single-cell RNA-sequencing analysis. Weight gain was significant by 3 weeks in HFD mice, and by 10 weeks all HFD groups had gained 20 g. HFD females (15 weeks) had increased energy expenditure and decreased activity. All HFD groups showed increases in serum leptin and decreases in adiponectin. HFD caused increased inflammatory markers: interleukin-6, resistin, monocyte chemoattractant protein-1, and tumor necrosis factorα. HFD males and females also had increased insulin and increased TSH, and HFD females had decreased serum prolactin and growth hormone pulse amplitude. Pituitary single-cell transcriptomics revealed modest or no changes in pituitary cell gene expression from HFD males after 10 or 15 weeks or from HFD females after 10 weeks. However, HFD females (15 weeks) showed significant numbers of differentially expressed genes in lactotropes and pituitary stem cells. Collectively, these studies reveal that pituitary cells from males appear to be more resilient to the oxidative stress of obesity than females and identify the most vulnerable pituitary cell populations in females.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1945-7170 0013-7227 1945-7170
DOI:	10.1210/endocr/bqad191