Batotin Inhibition to Restore Leptin Sensitivity in Obesity
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Solution Overview
Problem
Leptin resistance in individuals with diet-induced obesity leads to ineffective leptin treatment outcomes, including increased food intake and body weight gain, and impaired glycemic control, with peripheral tissues' secretory role in antagonizing leptin signaling remaining poorly understood.
Innovation Solution
Administration of batotin, an 8 kD adipokine selectively expressed in adipose tissue and liver, which binds to leptin receptors to suppress leptin signaling, promoting food intake and body weight gain, or use of batotin inhibitors to treat obesity and diabetes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If leptin treatment is administered to individuals with diet-induced obesity, then glycemic control may be improved, but food intake increases and body weight gain occurs due to leptin resistance
Solution Approach 1:
The patent introduces an antibody as an intermediary substance that specifically binds to batotin, preventing batotin from suppressing leptin signaling. This intermediary approach allows selective blockade of the harmful orexigenic effect while preserving the beneficial metabolic effects of leptin treatment
Solution Approach 2:
Instead of directly enhancing leptin signaling (which causes weight gain), the invention inverts the approach by selectively blocking the negative regulator (batotin). This indirect activation of leptin signaling through inhibition of its suppressor achieves weight loss while maintaining glycemic control
2Quantity of substance
If batotin is administered to promote weight gain in underweight subjects, then body weight and food intake increase, but leptin signaling is suppressed
Solution Approach 1:
The antibody serves as a selective intermediary that blocks batotin's interaction with leptin receptors, allowing leptin signaling to proceed effectively while still permitting batotin-mediated appetite stimulation when needed
3Loss of information
If peripheral tissues are targeted to understand antagonism of leptin signaling, then mechanism of leptin resistance is elucidated, but treatment complexity increases
Solution Approach 1:
The patent extracts and isolates the specific mechanism of leptin resistance by identifying batotin as the key antagonistic factor produced by peripheral tissues. This extraction of the core mechanism simplifies the treatment approach to targeting a single molecule with a monoclonal antibody
Solution Approach 2:
The monoclonal antibody acts as a targeted intermediary that specifically neutralizes batotin, providing a simplified treatment approach that addresses the root cause of leptin resistance without requiring complex multi-target interventions
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Batotin effectively alters leptin resistance, treating obesity and diabetes by increasing food intake and body weight in underweight subjects, and reducing food intake and weight in obese subjects, while improving glycemic control.
Implementation Method 1
Batotin, acting as an orexigenic hormone, binds to leptin receptor to suppress leptin signaling
Implementation Method 2
upon binding of leptin, the LepRb receptor dimerizes and undergoes a conformational change; this leads to the activation of multiple kinase pathways
Implementation Method 3
Activated JAK2 phosphorylates STAT3, which in turn translocates into nucleus to regulate expression of target genes
Data Source
AI summary
Methods for altering leptin resistance and the hormonal control of energy balance, and methods for treating obesity and diabetes, as well as promoting weight gain, using batotin and batotin inhibitors.