Abstract
Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug-target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus—derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A—positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability.
Highlights
The obesity pandemic is a predominant source of health problems worldwide, especially in the developed countries
We developed immortalized adult mouse hypothalamus—derived cell lines with moderate responsiveness to leptin; these cells could be used in the development of cell-based assay systems to evaluate leptin resistance
Fluorescence was detected in the neuron specific enolase (NSE) positive cells (Fig 1i, 1j and 1k) in the median eminence and in the arcuate nucleus of mediobasal hypothalamus (Fig 1l), indicating that CreERT2 functions in neural cells following tamoxifen administration
Summary
The obesity pandemic is a predominant source of health problems worldwide, especially in the developed countries. Obesity causes diseases such as diabetes, dyslipidemia, hypertension, cardiovascular diseases, osteoarthritis, and cancer, resulting in increased morbidity and mortality. Current therapeutic options include dieting, exercise, cognitive behavioral therapy, anti-obesity drugs, and bariatric surgery. These therapies have some beneficial effects on weight reduction, but with the exception of bariatric surgery, their effects are often limited and short-term. Several types of anti-obesity drugs are commercially available, including lipase inhibitors, dopamine and noradrenaline reuptake inhibitors, anti-convulsants, and serotonin receptor.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
