Thermogenesis of brown adipose tissues (BAT) provides metabolic benefits against pathological conditions such as Type 2 diabetes, obesity, cardiovascular diseases, and cancer. The thermogenic function of BAT relies on mitochondria, but whether mitochondrial remodeling is required for the beneficial effects of BAT remains unclear. We have recently identified FAM210A as a BAT-enriched mitochondrial protein essential for cold-induced thermogenesis through the modulation of OPA1-dependent cristae remodeling. Here we report a key role of FAM210A in the systemic response to high-fat diet (HFD). We discovered that HFD suppressed FAM210A expression, associated with excessive OPA1 cleavage in BAT. Ucp1-Cre-driven BAT-specific Fam210a knockout (Fam210aUKO) similarly elevates OPA1 cleavage, accompanied by whitening of BAT. When subjected to HFD, the Fam210aUKO mice gained similar fat mass as sibling control mice, but developed glucose intolerance, insulin resistance, and liver steatosis. The metabolic dysfunction was associated with an overall increased lipid content in both liver and BAT. Additionally, Fam210aUKO leads to inflammation in white adipose tissues. These data demonstrate that FAM210A in BAT is necessary for counteracting HFD-induced metabolic dysfunction but not obesity.

中文翻译：

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小鼠棕色脂肪细胞中 FAM210A 的消融加剧了高脂肪饮食诱导的代谢功能障碍


棕色脂肪组织 （BAT） 的产热对 2 型糖尿病、肥胖、心血管疾病和癌症等病理状况提供代谢益处。BAT 的产热功能依赖于线粒体，但 BAT 的有益作用是否需要线粒体重塑仍不清楚。我们最近确定 FAM210A 是一种富含 BAT 的线粒体蛋白，通过调节 OPA1 依赖性嵴重塑对冷诱导的产热至关重要。在这里，我们报道了 FAM210A 在对高脂饮食 （HFD） 的全身反应中的关键作用。我们发现 HFD 抑制了 FAM210A 表达，这与 BAT 中过度的 OPA1 切割有关。Ucp1-Cre 驱动的 BAT 特异性 Fam210a 敲除 （Fam210aUKO） 同样升高 OPA1 切割，伴有 BAT 变白。当接受 HFD 时，Fam210aUKO 小鼠获得了与兄弟姐妹对照小鼠相似的脂肪量，但出现了葡萄糖耐受不良、胰岛素抵抗和肝脂肪变性。代谢功能障碍与肝脏和 BAT 中脂质含量的总体增加有关。此外，Fam210aUKO 会导致白色脂肪组织发炎。这些数据表明，BAT 中的 FAM210A 对于抵消 HFD 诱导的代谢功能障碍是必需的，但不是肥胖所必需的。