Depot-dependent peroxisome response in the rat white adipose tissue under hypothyroidism

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The effect of thyroid hormones (TH) on metabolism and energy balance relies on their impact on lipid storage in adipose tissue (AT). Since peroxisomes play a key role in lipid metabolism in white AT, hypothyroidism may critically influence peroxisome population/dynamics. This study aimed to determine depot- and time-dependent effects of methimazole-induced hypothyroidism on peroxisome biogenesis and remodeling in rat white AT. Hypothyroidism was induced using 0.04% methimazole over 7, 15, or 21 days. We show that hypothyroidism affects peroxisome biogenesis in subcutaneous AT (SAT) and visceral AT (VAT) (mesenteric-mVAT, retroperitoneal-rVAT and gonadal-gVAT) in a depot-specific manner. Firstly, although a gradual increase in peroxisomal number is present in all of the AT depots examined, the time course differs. Secondly, according to ultrastructural and protein expression analyses of Pex11β, Pex19, and PPARα, biogenesis pathways are switching from canonical to de novo pathway in hypothyroidism, again distinctively across particular depots. Furthermore, this is accompanied by the emergence of unusual peroxisomal structures (pexopodium) infiltrating lipid bodies in VAT. The absence of acyl-coenzyme A oxidase 1 (ACOX1) suggests that such structures may develop as a consequence of uncoordinated oxidation of accumulated fatty acids in VAT. The presence of pexopodium was increased from day 15 of hypothyroidism in mVAT. However, this increase was transient in rVAT and gVAT, indicating different peroxisomal dynamics between VAT depots during the monitored period of induction. Pexopodium-like structures were not observed in SAT. Our results identify peroxisomal remodeling as a previously underappreciated component of adipose tissue plasticity in hypothyroidism. Discrete temporal and depot-specific responses, including the formation of pexopodia in VAT, underscore the functional heterogeneity of white AT depots and suggest that peroxisomal dynamics may contribute to regional metabolic vulnerability under thyroid hormone deficiency over the time.

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