Biology subjects

Colman, R. J.

Publications and source records attributed to Colman, R. J..

4 recordsLinked to original sources

bioRxiv2025

Caloric restriction reprograms adipose tissues in rhesus monkeys

Caloric restriction (CR) is a dietary intervention that delays the onset of age-related diseases and enhances survival in diverse organisms, and although changes in adipose tissues have been implicated in the beneficial effects of CR the molecular details are unknown. Here we show shared and depot-specific adaptations to life-long CR in subcutaneous and visceral adipose depots taken from advanced age male rhesus monkeys. Differential gene expression and pathway analysis identified key differences between the depots in metabolic, immune, and inflammatory pathways. In response to CR, RNA processing and proteostasis-related pathways were enriched in both depots but changes in metabolic, growth, and inflammatory pathways were depot-specific. Commonalities and differences that distinguish adipose depots are shared among monkeys and humans and the response to CR is highly conserved. These data reveal depot-specificity in adipose tissue adaptation that likely reflects differences in function and contribution to age-related disease vulnerability. In BriefRhesus monkey adipose tissues are highly responsive to long-term caloric restriction, although the response is depot-specific. Shared features include proteostasis and RNA processing pathways, whereas metabolic pathways, alterations in processes influenced by growth signaling, and changes in exon usage were depot-specific. The impact of CR on subcutaneous adipose tissue is highly conserved between monkeys and humans. HighlightsO_LIAt the transcript level, SAT and VAT taken from the same animals show modest specialization, primarily in metabolic and immune pathways. C_LIO_LIThe transcriptome of SAT is more responsive to CR than that of VAT, with depot-specific differences in metabolic adaptation and cell type composition. C_LIO_LIRNA processing pathways are engaged by CR and transcript isoforms are enriched in both depots, but differential exon usage is limited to SAT. C_LIO_LIAdipose reprogramming is linked to CR induced differences in body composition and systemic indices of health. C_LIO_LIThe impact of CR on subcutaneous adipose tissue is highly similar between monkeys and humans. C_LI

genomics↗

bioRxiv2023

Mass spectrometry-based multi-omics identifies metabolic signatures of sarcopenia in rhesus monkey skeletal muscle

Sarcopenia is a progressive disorder characterized by age-related loss of skeletal muscle mass and function. Although significant progress has been made over the years to identify the molecular determinants of sarcopenia, the precise mechanisms underlying the age-related loss of contractile function remains unclear. Advances in omics technologies, including mass spectrometry-based proteomic and metabolomic analyses, offer great opportunities to better understand sarcopenia. Herein, we performed mass spectrometry-based analyses of the vastus lateralis from young, middle-aged, and older rhesus monkeys to identify molecular signatures of sarcopenia. In our proteomic analysis, we identified numerous proteins that change with age, including those involved in adenosine triphosphate and adenosine monophosphate metabolism as well as fatty acid beta oxidation. In our untargeted metabolomic analysis, we identified multiple metabolites that changed with age largely related to energy metabolism including fatty acid beta oxidation. Pathway analysis of age-responsive proteins and metabolites revealed changes in muscle structure and contraction as well as lipid, carbohydrate, and purine metabolism. Together, this study discovers new metabolic signatures and offer new insights into the molecular mechanism underlying sarcopenia for the evaluation and monitoring of therapeutic treatment of sarcopenia. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=67 SRC="FIGDIR/small/551315v1_ufig1.gif" ALT="Figure 1"> View larger version (15K): org.highwire.dtl.DTLVardef@1dc0addorg.highwire.dtl.DTLVardef@14d73b8org.highwire.dtl.DTLVardef@1e8733forg.highwire.dtl.DTLVardef@1e65408_HPS_FORMAT_FIGEXP M_FIG C_FIG Graphical Abstract

biochemistry↗

bioRxiv2021

Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

The loss of skeletal muscle function with age, known as sarcopenia, significantly reduces independence and quality of life and can have significant metabolic consequences. Although exercise is effective in treating sarcopenia it is not always a viable option clinically, and currently there are no pharmacological therapeutic interventions for sarcopenia. Here we show that chronic treatment with pan-adiponectin receptor agonist AdipoRon improved muscle function in male mice by a mechanism linked to skeletal muscle metabolism and tissue remodeling. In aged mice, 6 weeks of AdipoRon treatment improved skeletal muscle functional measures in vivo and ex vivo. Improvements were linked to changes in fiber type, including an enrichment of oxidative fibers, and an increase in mitochondrial activity. In young mice, 6 weeks of AdipoRon treatment improved contractile force and activated the energy sensing kinase AMPK and the mitochondrial regulator PGC-1a (peroxisome proliferator activated receptor gamma coactivator 1 alpha). In cultured cells, the AdipoRon induced stimulation of AMPK and PGC-1a was associated with increased mitochondrial membrane potential, reorganization of mitochondrial architecture, increased respiration, and increased ATP production. Furthermore, the ability of AdipoRon to stimulate AMPK and PGC1a was conserved in nonhuman primate cultured cells. These data show that AdipoRon is an effective agent for the prevention of sarcopenia in mice and indicate that its effects translate to primates, suggesting it may also be a suitable therapeutic for sarcopenia in clinical application.

physiology↗

bioRxiv2021

Development and Validation of an LC-MS/MS Based Quantitative Assay for Marmoset Insulin

IntroductionInsulin is a peptide hormone that is secreted by the {beta} cells of the pancreas and is essential to the metabolism of carbohydrates, fats, and proteins in the body. The marmoset insulin peptide is not homologous with human insulin and therefore commonly available assays do not work for this species. Due to the increasing popularity of marmoset research, a simple, specific assay for the quantitation of marmoset insulin is needed. This study aimed to develop and validate a bottom-up proteomic workflow with trypsin digestion and analysis using LC coupled with triple quadrupole mass spectrometry (LC-MS/MS). MethodsMarmoset serum proteins were subjected to denaturation, reduction, and enzymatic cleavage to extract a unique, 7 amino acid peptide for quantitation of marmoset insulin.Resolution of the peptide was achieved by LC-MS/MS using electrospray ionization operating in positive mode. Calibration was achieved by aliquot dilution of fully synthetic marmoset insulin tryptic peptide into macaque serum. A stable-isotope labeled (13C, 15N) synthetic marmoset insulin tryptic peptide was used as internal standard. ResultsThe assay was fully validated according to bioanalytical method validation guidelines for linearity, precision, and dilution linearity using purified marmoset insulin. The limit of detection was 4.28 pmol/L and the limit of quantitation was 8.62 pmol/L. Biological validation was achieved by comparison of samples previously run by radioimmunoassay and measurement of the marmoset insulin response to glucose via an oral glucose tolerance test (OGTT). The physiological range of marmoset insulin was shown to be 84.5 to 1222 pmol/L. ConclusionsThis paper presents a simple, reproducible method to measure marmoset insulin using LC-MS/MS.

biochemistry↗