Dysregulated adipocyte physiology leads to imbalanced energy storage, obesity, and associated diseases, imposing a costly burden on current health care. Cannabinoid receptor type-1 (CB1) plays a crucial role in controlling energy metabolism through central and peripheral mechanisms. In this work, adipocyte-specific inducible deletion of the CB1 gene (Ati-CB1–KO) was sufficient to protect adult mice from diet-induced obesity and associated metabolic alterations and to reverse the phenotype in already obese mice. Compared with controls, Ati-CB1–KO mice showed decreased body weight, reduced total adiposity, improved insulin sensitivity, enhanced energy expenditure, and fat depot–specific cellular remodeling toward lowered energy storage capacity and browning of white adipocytes. These changes were associated with an increase in alternatively activated macrophages concomitant with enhanced sympathetic tone in adipose tissue. Remarkably, these alterations preceded the appearance of differences in body weight, highlighting the causal relation between the loss of CB1 and the triggering of metabolic reprogramming in adipose tissues. Finally, the lean phenotype of Ati-CB1–KO mice and the increase in alternatively activated macrophages in adipose tissue were also present at thermoneutral conditions. Our data provide compelling evidence for a crosstalk among adipocytes, immune cells, and the sympathetic nervous system (SNS), wherein CB1 plays a key regulatory role.

中文翻译：

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脂肪细胞大麻素受体 CB1 调节能量稳态和交替激活的巨噬细胞

脂肪细胞生理失调会导致能量储存失衡、肥胖和相关疾病，给当前的医疗保健带来代价高昂的负担。大麻素受体 1 型 (CB1) 在通过中枢和外周机制控制能量代谢中起着至关重要的作用。在这项工作中， CB1基因 ( Ati-CB1-KO )的脂肪细胞特异性可诱导缺失足以保护成年小鼠免受饮食诱导的肥胖和相关的代谢改变，并逆转已经肥胖的小鼠的表型。与对照相比，Ati-CB1-KO小鼠表现出体重下降、总肥胖减少、胰岛素敏感性提高、能量消耗增加以及脂肪库特异性细胞重塑导致能量储存能力降低和白色脂肪细胞褐变。这些变化与交替激活的巨噬细胞增加有关，同时脂肪组织中的交感神经张力增强。值得注意的是，这些改变先于体重差异的出现，突出了CB1的丢失与脂肪组织中代谢重编程的触发之间的因果关系。最后，Ati-CB1-KO的瘦表型小鼠和脂肪组织中交替激活的巨噬细胞的增加也存在于热中性条件下。我们的数据为脂肪细胞、免疫细胞和交感神经系统 (SNS) 之间的串扰提供了令人信服的证据，其中CB1起着关键的调节作用。