FGF8b Polypeptide Inducing White to Brown Adipocyte Conversion

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Solution Overview

Problem

Current treatments for obesity and related metabolic disorders, such as diabetes and dyslipidemia, are inadequate due to the limited amount of brown adipose tissue in adults, particularly overweight individuals, which hinders effective thermogenesis and energy expenditure.

Innovation Solution

The use of paracrine FGFs, specifically FGF8b and FGF8f, to induce the differentiation or conversion of white adipocytes to brown adipocytes, increasing the mass of active brown adipose tissue through local administration, particularly in visceral adipose tissue, thereby enhancing energy dissipation and improving metabolic health.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for obesity and metabolic disorders are used, then treatment is provided, but the treatments are inadequate due to limited brown adipose tissue mass

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidbrown adipose tissue mass
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the biological state of adipose tissue by inducing differentiation of white adipocytes into brown adipocytes through FGF8b treatment, thereby transforming the tissue's functional properties from energy storage to energy dissipation

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses FGF8b as an intermediary substance to mediate the conversion of white adipose tissue to brown adipose tissue, enabling therapeutic effects without directly manipulating the adipocytes themselves

Inventive Principle:
Principle #24Intermediary (Mediator)

2Use of energy by moving object

If white adipose tissue is converted to brown adipose tissue, then energy expenditure is enhanced, but this requires inducing differentiation of adipocytes

Engineering Contradiction:
Improveenergy expenditureVSAvoiddifferentiation process complexity
Core Design Contradiction:
Use of energy by moving objectVSDevice complexity

Solution Approach 1:

The patent enables white adipocytes to self-differentiate into brown adipocytes through FGF8b treatment, utilizing the cells' inherent plasticity and differentiation capacity without requiring external cellular manipulation techniques

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The patent changes the phenotypic parameters of adipocytes by inducing expression of brown adipocyte-specific genes and proteins, thereby transforming the tissue's metabolic function from anabolic to catabolic

Inventive Principle:
Principle #35Parameter changes

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

This approach effectively increases brown adipose tissue, leading to improved energy expenditure, weight loss, and enhanced insulin sensitivity, providing a therapeutic means for obesity, diabetes, and dyslipidemia by converting energy-storing white fat into energy-dissipating brown fat, thus addressing the limitations of existing treatments.

Implementation Method 1

induce the differentiation or conversion of white adipocytes to brown adipocytes

Methodology Applied
Scientific EffectCell differentiation:

Implementation Method 2

The primary function of brown adipose tissue is to produce body heat in mammals without the necessity to shiver

Methodology Applied
Scientific EffectThermogenesis:

Implementation Method 3

body heat is produced by signaling the mitochondria to allow protons to run back along the proton gradient without producing ATP (proton leak). This is realized by the uncoupling protein 1 (Ucp1 or thermogenin)

Methodology Applied
Scientific EffectUncoupling protein 1-mediated proton leak:

Data Source

PatentEP3104873B1FGF-8 for use in treating diseases or disorders of energy homeostasis
Publication Date: 2019.09.04 TECHNISCHE UNIVERSITAT MUNCHEN
  • EP3104873B1 patent drawingFigure 1A
  • EP3104873B1 patent drawingFigure 1B~1C
  • EP3104873B1 patent drawingFigure 2A

AI summary

The present invention relates to polypeptides for use in treating diseases or disorders of energy homeostasis such as obesity, dyslipidemia, diabetes, insulin resistance, hyperglycemia or the metabolic syndrome. The invention also relates to polynucleotides encoding said polypeptides for use in treating diseases or disorders of energy homeostasis. Also provided by the present invention are pharmaceutical compositions comprising said polypeptides and polynucleotides for use in treating diseases or disorders of energy homeostasis. Said polypeptides, polynucleotides and pharmaceutical compositions may be administered locally, in particular locally into the visceral adipose tissue. Another aspect of the invention relates to a cosmetic product and the use of said cosmetic product for reducing body weight, in particular for reducing abdominal adipose tissue.