Obesity, a pathological accumulation of body fat, is a global health concern linked to cardiovascular disease, diabetes, infertility and several cancers [1]. Adipose tissue, commonly referred to as 'fat', plays essential roles in regulating various physiological processes, including energy metabolism, food intake, thermogenesis and insulin responses. It is broadly classified as two types, white adipose tissue (WAT) and brown adipose tissue (BAT). WAT, characterized by sparse mitochondria and large lipid droplets, specializes in energy storage and adipokine secretion (e.g., leptin). Subcutaneous WAT (sWAT) or gonadal WAT (gWAT) represent its primary deposits. In contrast, interscapular BAT is distinguished by high mitochondria density and Uncoupling Protein 1 (UCP1), which can exert thermogenesis [2]. Adipose tissue plasticity enables reversible transformation between WAT and BAT. WAT browning can offer protection against weight gain and metabolic disorders by elevating energy expenditure, thermogenesis and insulin sensitivity [3,4]. Identifying regulaters of WAT browning and energy metabolism is crucial for developing obesity therapies.

Oxytocin Receptor (OXTR), a G-protein coupled receptor, is involved in thermogenesis. OXTR is widely expressed in mammalian tissues, including the brain, reproductive organs, mammary gland, and bone [5]. Its ligand, oxytocin (OXT), is synthesized in the neurons of the paraventricular nucleus (PVN) and the supraoptic nucleus of the hypothalamus and secreted by the posterior lobe [6]. OXTR, in response to OXT binding, processes and transfers signals into the cytoplasm to modulate the downstream events. OXT/OXTR system is implicated in parturition, milk ejection, mammary gland development, bone formation, social behaviors, and cancer progression [[7], [8], [9]]. In mice, hypothalamic OXT-producing neurons in the PVN connect to pancreatic β-cells via sympathetic nerves, ultimately affecting insulin release [10]. Cold exposure upregulates OXT and OXTR expression in BAT and brain [11]. Both Oxtr-knockout mice (Oxtr−/−) and Oxt-knockout (Oxt−/−) exhibit impaired cold-induced thermogenesis, diabetes, and late-onset of obesity [[12], [13], [14]], while exogenous OXT can promote thermogenesis and mitigates metabolic dysfunctions [15,16]. These evidences indicate the significant role of OXT system in energy metabolism. Here, we investigated the OXTR's effects in energy metabolism and adipose development using the ++Oxtr mouse model.