👤 Moeko Miyamori

Melanocortin-4 receptor (Mc4r) is a G protein-coupled receptor that controls systemic energy balance by regulating food intake and energy expenditure. Although the detailed molecular mechanism remains unclear, the activation of cAMP signaling in Mc4r-expressing cells reportedly suppresses food intake and increases energy expenditure. CREBP-regulated transcriptional coactivator-1 (CRTC1) is selectively expressed in neuronal cells and participates in transcriptional control, thereby contributing to neuronal plasticity and energy homeostasis. Considering the cAMP-dependent regulation of CRTC1 activity, CRTC1 in Mc4r-expressing cells may contribute to energy balance regulation through the melanocortin pathway. In this context, we examined the physiological contribution of CRTC1 in Mc4r-expressing cells to energy metabolism. In this study, mice with CRTC1 deficiency in Mc4r-expressing cells exhibited 1) modest obesity, glucose intolerance, insulin resistance, hyperinsulinemia, and hyperlipidemia; 2) decreased systemic energy expenditure and thermogenesis; 3) suppression of melanocortin agonist-induced adaptation of energy expenditure and food intake; 4) impaired thermogenic programs and oxidative pathway in brown adipose tissue and skeletal muscle; and 5) enhanced lipogenic programs in the liver and white adipose tissue. These results provide novel insights into the molecular mechanisms underlying the regulation of energy balance by the melanocortin system. Show less

Primary haematological neoplasms of the larynx are uncommon; therefore, information regarding their epidemiology is limited and the diagnosis of histological types requires careful consideration. The current study describes the case of a 72-year-old male patient with primary laryngeal lymphoplasmacytic lymphoma (LPL) that was difficult to distinguish from plasmacytoma. Imaging examinations of the neck revealed a mass in the right laryngeal folds, 25×12×25 mm in size, which was surgically resected by direct laryngoscopy. Histopathologically, the mass showed diffuse proliferation of plasma cells with CD138 (+) and IgG (+) in the submucosal stroma. Flow cytometry revealed the tumour was positive for CD19 and negative for CD56. Based on these findings, the final diagnosis was confirmed as LPL, albeit similar to plasmacytoma regarding phenotypic features. There was no evidence of local or systemic recurrence following surgery, and the patient has been followed up without additional treatment. This case highlights the unique presentation of laryngeal lymphoma mimicking solitary plasmacytoma. The key factor in the diagnosis was the expression pattern of surface antigen markers. Show less

Melanocortin-4 receptor (MC4R) is a critical regulator of appetite and energy expenditure in rodents and humans. MC4R deficiency causes hyperphagia, reduced energy expenditure, and impaired glucose metabolism. Ligand binding to MC4R activates adenylyl cyclase, resulting in increased levels of intracellular cyclic adenosine monophosphate (cAMP), a secondary messenger that regulates several cellular processes. Cyclic adenosine monophosphate responsive element-binding protein-1-regulated transcription coactivator-1 (CRTC1) is a cytoplasmic coactivator that translocates to the nucleus in response to cAMP and is reportedly involved in obesity. However, the precise mechanism through which CRTC1 regulates energy metabolism remains unknown. Additionally, there are no reports linking CRTC1 and MC4R, although both CRTC1 and MC4R are known to be involved in obesity. Here, we demonstrate that mice lacking CRTC1, specifically in MC4R cells, are sensitive to high-fat diet (HFD)-induced obesity and exhibit hyperphagia and increased body weight gain. Moreover, the loss of CRTC1 in MC4R cells impairs glucose metabolism. MC4R-expressing cell-specific CRTC1 knockout mice did not show changes in body weight gain, food intake, or glucose metabolism when fed a normal-chow diet. Thus, CRTC1 expression in MC4R cells is required for metabolic adaptation to HFD with respect to appetite regulation. Our results revealed an important protective role of CRTC1 in MC4R cells against dietary adaptation. Show less

The melanocortin 4 receptor (MC4R) plays an important role in the regulation of appetite and energy expenditure in humans and rodents. Impairment of MC4R signaling causes severe obesity. MC4R mainly couples to the G-protein G Show less