Activating nonshivering thermogenesis in brown adipose tissue (BAT) is a promising strategy to prevent obesity. This study investigated whether quercetin supplementation improves obesity in mice by increasing nonshivering thermogenesis in BAT and white adipose tissue (WAT) browning. Compared to HFD-fed mice, mice fed a high-fat diet supplemented with 1% quercetin (HFDQ) had reduced body weight and total plasma cholesterol. In HFDQ-fed mice, retroperitoneal WAT (RWAT) weight was decreased, and browning effect and lipolysis were increased. HFDQ-fed mice had increased expression of nonshivering thermogenesis genes in BAT, including uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α), cell death-inducing DFFA-like effector A (CIDEA), and mitochondrial transcriptional factor A (mtTFA). Quercetin supplementation increased genes and proteins in β₃-adrenergic receptor (ADRB3), p38 mitogen-activated protein kinase (MAPK), and AMP-activated protein kinase (AMPK) pathways in HFD-fed mice, which were suppressed by an AMPK inhibitor or an ADRB3 antagonist. Energy expenditure and core body temperature were not changed by quercetin, but physical activity was increased in HFDQ mice during dark periods at room and cold temperatures. Quercetin also decreased the Firmicutes to Bacteroidetes ratio and increased short-chain fatty acid (SCFA) production in the feces of HFD-fed mice. In summary, quercetin supplementation in HFD-fed mice may attenuate obesity. Although the study did not show consistency in data at molecular and pathphysiological levels between BAT function and obesity, it also shows promising health effects of quercetin, accompanied by improved physical activity and gut microbiota dysbiosis.

激活棕色脂肪组织 (BAT) 中的非颤抖产热是预防肥胖的一种很有前景的策略。本研究调查了槲皮素补充剂是否通过增加 BAT 中的非颤抖产热和白色脂肪组织 (WAT) 褐变来改善小鼠的肥胖症。与喂食 HFD 的小鼠相比，喂食补充有 1% 槲皮素 (HFDQ) 的高脂肪饮食的小鼠体重和血浆总胆固醇降低。在 HFDQ 喂养的小鼠中，腹膜后 WAT (RWAT) 重量降低，褐变效应和脂解作用增加。HFDQ 喂养的小鼠在 BAT 中非颤抖产热基因的表达增加，包括解偶联蛋白 1 (UCP1)、过氧化物酶体增殖物激活受体-γ 共激活因子 1α (PGC1α)、诱导细胞死亡的 DFFA 样效应子 A (CIDEA) 和线粒体转录因子 A (mtTFA)。₃- 肾上腺素能受体 (ADRB3)、p38 丝裂原活化蛋白激酶 (MAPK) 和 HFD 喂养小鼠中的 AMP 活化蛋白激酶 (AMPK) 通路，这些通路被 AMPK 抑制剂或 ADRB3 拮抗剂抑制。槲皮素不会改变能量消耗和核心体温，但在室温和低温下的黑暗时期，HFDQ 小鼠的体力活动增加。槲皮素还降低了 HFD 喂养小鼠粪便中厚壁菌门与拟杆菌门的比率，并增加了短链脂肪酸 (SCFA) 的产生。总之，在 HFD 喂养的小鼠中补充槲皮素可能会减轻肥胖。尽管该研究未显示 BAT 功能与肥胖之间分子和病理生理学水平的数据一致性，但它也显示了槲皮素对健康的有希望的影响，