Thermogenic stimulation with cold exposure and pioglitazone upregulated intracellular peptides derived from hemoglobin, which enhanced thermogenic and adipogenic markers in brown and white adipocytes.
Does thermogenic stimulation with cold exposure and pioglitazone modulate functional intracellular peptide levels in mice brown and white adipose tissues?
Intracellular peptides, primarily derived from hemoglobin, are upregulated by thermogenic stimuli and act as modulators of thermogenic activity in brown and beige adipocytes.
Brown adipose tissue (BAT) and beige adipocytes within white adipose tissue (WAT) mediate nonshivering thermogenesis through uncoupling protein 1 (UCP1). Here, we characterized the peptidome of interscapular BAT and inguinal WAT under thermogenic stimulation combining cold exposure and pharmacological activation of PPARγ by pioglitazone. C57BL/6 mice were housed at 21 °C or 7 °C for 15 days and treated with pioglitazone (30 mg/kg/day) or vehicle. Mass spectrometry identified 39 peptides in BAT and 95 in WAT, most derived from hemoglobin alpha and beta subunits and upregulated under thermogenic conditions. Twenty-four peptides were common to both tissues, and eleven upregulated peptides (P1–P11) were further investigated in cultured adipocytes and isolated mitochondria. Peptide P8 increased the expression of thermogenesis and adipogenesis-related genes (UCP1, PGC1α, Cpt1a, and FABP4) in brown adipocytes, while P1 and P11 enhanced these genes in white adipocytes. Peptides P2, P4, P6, and P9 increased mitochondrial oxygen consumption in BAT. Collectively, these findings highlight a novel role of intracellular peptides as modulators of thermogenic activity in brown and beige adipocytes and provide novel insights into their biological and therapeutic relevance. • Peptidome analyses identified novel candidates with clinical potential for metabolic diseases. • Cold exposure increased the relative levels of most identified peptides in BAT and WAT. • Hemoglobin proteins (HBA, HBB1) are upregulated by thermogenic stimulus and represent the main source of intracellular peptides. • Intracellular peptides modulate thermogenic and adipogenic markers in brown and white adipocytes and BAT mitochondrial respiration.
Valdivia et al. (Wed,) conducted a other in Thermogenesis in adipose tissue. Cold exposure and pioglitazone vs. 21 °C and vehicle was evaluated on Peptidome characterization and expression of thermogenesis/adipogenesis-related genes. Thermogenic stimulation with cold exposure and pioglitazone upregulated intracellular peptides derived from hemoglobin, which enhanced thermogenic and adipogenic markers in brown and white adipocytes.