Abstract

In mammals, peripheral serotonin is involved in regulating energy balance. Herein, we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin. Holstein bull calves (21 ± 2 days old) were fed milk replacer supplemented with saline (CON, 8 mL/day n = 4) or 5-hydroxytryptophan (5-HTP, 90 mg/day, n = 4) for 10 consecutive days. Calves were euthanized on d10 to harvest adipose and muscle for RNA-Sequencing and histological analyses. Twenty-two genes were differentially expressed in adipose, and 33 in muscle. Notably, Interferon gamma inducible protein-47 was highly expressed and upregulated in muscle and adipose (avg. log FC = 6.5). Enriched pathways in adipose tissue revealed serotonin’s participation in lipid metabolism and PPAR signaling. In muscle, enriched pathways were related to histone acetyltransferase binding, Jak-STAT signaling, PI3K-Akt signaling and cell proliferation. Supplementation of 5-HTP increased cell proliferation and total cell number in adipose and muscle. Adipocyte surface area was smaller and muscle fiber area was not different in the 5-HTP group. Manipulating the serotonin pathway, through oral supplementation of 5-HTP, influences signaling pathways and cellular processes in adipose and muscle related to endocrine and metabolic functions which might translate into improvements in calf growth and development.

Highlights

  • IntroductionPeripheral serotonin is involved in regulating energy balance. we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin

  • In mammals, peripheral serotonin is involved in regulating energy balance

  • We hypothesize that increasing calves’ serotonin bioavailability would promote subcutaneous white adipose tissue (WAT) and gluteus medius skeletal muscle cell proliferation and growth, and trigger expression of genes related to primary endocrine and metabolic functions

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Summary

Introduction

Peripheral serotonin is involved in regulating energy balance. we characterized the transcriptomic profile and microstructure of adipose and muscle in pre-weaned calves with increased circulating serotonin. Manipulating the serotonin pathway, through oral supplementation of 5-HTP, influences signaling pathways and cellular processes in adipose and muscle related to endocrine and metabolic functions which might translate into improvements in calf growth and development. In fasted mice, gut-derived peripheral serotonin stimulates white adipose tissue lipolysis and mobilizes circulating free fatty acids and glycerol by activating 5-HT2B in a­ dipocytes[3,18]. The objective of this study was to investigate cellular processes and transcriptomic alterations in adipose and muscle tissues of pre-weaned dairy calves with elevated peripheral serotonin concentrations. We hypothesize that increasing calves’ serotonin bioavailability would promote subcutaneous white adipose tissue (WAT) and gluteus medius skeletal muscle cell proliferation and growth, and trigger expression of genes related to primary endocrine and metabolic functions. Deciphering serotonin’s participation in metabolic tissues might aid in the regulation of energy-demanding metabolic changes necessary for calf growth during the pre-weaning developmental phase

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