Identification of biomarkers of brown adipose tissue aging highlights the role of dysfunctional energy and nucleotide metabolism pathways

Abstract

Brown adipose tissue function declines during aging and may contribute to the onset of metabolic disorders such as diabetes and obesity. Only limited understanding of the mechanisms leading to the metabolic impairment of brown adipocytes during aging exists. To this end, interscapular brown adipose tissue samples were collected from young and aged mice for quantification of differential gene expression and metabolite levels. To identify potential processes involved in brown adipocyte dysfunction, metabolite concentrations were correlated to aging and significantly changed candidates were subsequently integrated with a non-targeted proteomic dataset and gene expression analyses. Our results include novel age-dependent correlations of polar intermediates in brown adipose tissue. Identified metabolites clustered around three biochemical processes, specifically energy metabolism, nucleotide metabolism and vitamin metabolism. One mechanism of brown adipose tissue dysfunction may be linked to mast cell activity, and we identify increased histamine levels in aged brown fat as a potential biomarker. In addition, alterations of genes involved in synthesis and degradation of many metabolites were mainly observed in the mature brown adipocyte fraction as opposed to the stromal vascular fraction. These findings may provide novel insights on the molecular mechanisms contributing to the impaired thermogenesis of brown adipocytes during aging.

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

“…The thermogenic activity of BAT is related to metabolic health and is impaired in obese individuals [ 12 ]. Body mass index (BMI) and age are inversely correlated with BAT activation [ 13 ]. BAT content declines in the obese and the brown fat cells acquire a white fat cell-like morphology [ 14 ].…”

Three-dimensional visualization of electroacupuncture-induced activation of brown adipose tissue via sympathetic innervation in PCOS rats

“…Adipose tissues play an important role in regulating systemic energy levels, especially BAT, which converts chemical energy into heat. Compared with WAT, the amount of BAT is lower and decreases with age [ 25 ]. However, long-term cold exposure can stimulate the proliferation and differentiation of mature BAT precursors, increase UCP1 expression, and increase the volume of BAT and heat production [ 26 ].…”

Propranolol normalizes metabolomic signatures thereby improving outcomes after burn

“…Hypoxanthine, glutamyl-proline, and threonyl-histidine are important metabolites in several processes, such as nucleotide synthesis, collagen formation, immune cell differentiation, and age-related adipose tissue dysfunctions. [24][25][26][27][28][29][30][31][32] Finally, we found several significant metabolites that are either downregulated or upregulated in burn patients. These compounds are mostly involved in energy metabolism and nucleotide metabolism (threonyl-histidine, methionyl-proline, cystine, uracil, VMA, 5-hydroxylysine, thymine) (Figs.…”

“…4). Hypoxanthine, glutamyl-proline, and threonyl-histidine are important metabolites in several processes, such as nucleotide synthesis, collagen formation, immune cell differentiation, and age-related adipose tissue dysfunctions 24–32 …”