Hepatic Dysfunctions in C57/BL6 mice after Liver-based POMC Overexpression

• Main Authors: Chuan-hsiu Lu, 呂鵑秀
• Other Authors: Ming-hong Tai
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/72558773649982927474

碩士 === 國立中山大學 === 生物科學系研究所 === 98 === The pro-opiomelanocortin (POMC) prohormone produces several biologically active peptides, including α-melanocyte-stimulating hormones (α-MSH, β-MSH, γ-MSH), corticotrophin (ACTH) and β-endorphin. POMC-expressing neurons in the brain play a major role in the control of pain, energy homeostasis, pigmentation, adrenocortical function, and sebaceous gland lipid production. Recently, the peripheral POMC system is under active investigation to delineate their pathogenic roles in metabolic diseases such as Cushing’s syndrome and obesity. In the present study, we employed adenovirus gene delivery system to achieve POMC overexpression in the livers of adult C57/BL6 mice. In the endocrine system of adrenal glands, hepatic POMC overexpression mice display hypertrophy the ACTH levels elevated concentrations in the blood, the ACTH receptor, melanocortin type 2 receptor (MC2-R) were decrease. This phenomenon explained the local adrenal gland tissue was inhibiting and feedback from central hypothalamic-pituitary- adrenal axis. Meanwhile, we investigated the islets of Langerhans in hepatic POMC overexpression mice, the insulin were disappear but the glucagon were constant, these reflect the blood sugar were loss of balance, maybe progress to metabolic syndrome. Subsequently, hepatic POMC overexpression resulted in liver injuries that the ALT and AST levels were significantly higher, the fat accumulation in the liver and the glycogen were diminished to nearly 1/4 of basal levels. Evidence the hepatic POMC overexpression induced inflammatory and fatty changes in the livers of mice. In summary, POMC gene delivery induces systemic POMC overexpression and results in fatty liver and adrenal dysfunction, which may facilitates a mice model for Cushing’s-like metabolic syndrome.