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SorCS1 for use in the treatment of obesity and overweight

An amino acid and pharmaceutical technology, applied in the application field of SorCS1 in the treatment of obesity and overweight

Inactive Publication Date: 2015-03-25
AARHUS UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Byetta is only approved and recommended for people with type 2 diabetes

Method used

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  • SorCS1 for use in the treatment of obesity and overweight
  • SorCS1 for use in the treatment of obesity and overweight
  • SorCS1 for use in the treatment of obesity and overweight

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0379] Example 1: Gene expression profiling of adipose tissue derived from SorCS1 knockout mice by PCR array

[0380] To examine the gene expression profile of SorCS1 knockout mice, microarray analysis was used to measure the expression of 84 genes related to mouse insulin signaling pathway and 84 genes related to mouse lipoprotein signaling & cholesterol metabolism. Microarray analysis was performed using RNA from adipose tissue of SorCS1 knockout wild-type obese mice. In practice, first-strand cDNA was synthesized from total RNA (Applied Life Systems) in adipose tissue of 50-week-old female mice (n = 3) SorCS1 knockout (- / -) and wild-type (+ / +). Then, superarrays of mouse insulin signaling pathway (PAMM-030A RT2Profiler PCR array) or B) mouse lipoprotein signaling & cholesterol metabolism (PAMM-080-A RT2Profiler PCR array) were prepared using the ABI7900 platform (Applied Life Systems) and SYBR Green / Rox PCR (SA Biosciences) treatment. The expression analysis was done with...

Embodiment 2

[0381] Example 2: Weight loss in diabetic db / db mice after overexpression of soluble SorCS1.

[0382] To assess the effect of soluble SorCS1 on body weight in an obese mouse model that spontaneously develops type 2 diabetes, a db / db mouse strain (BKS.Cg-m+ / +Lpr from Taconic db / BomTac). These mice lack leptin receptors, so the mice become obese and develop insulin resistance and eventually severe diabetes at 6-8 weeks of age.

[0383] Adenovirus expressing human soluble (hsol) SorCS1 or LacZ as a control were injected to examine the effect on weight. A recombinant adenovirus expressing human soluble SorCS1 (hsol.SorCS1) was produced as follows:

[0384] pcDNA3.1 / Zeo(-) / hsol.SorCS1 (amino acid 1-1100) encoding human soluble SorCS1 cDNA was digested with Pme1 and Apa1 and the fragment encoding hsol.SorCS1 was inserted into the shuttle plasmid pVQpacAd5CMVK-NPA (ViraQuest Company, North Liberty, IA). ViraQuest Corporation, North Liberty, IA, then used this shuttle plasmid to ...

Embodiment 3

[0386] Example 3: Reduced food intake and weight in diabetic db / db mice after overexpression of soluble SorCS1.

[0387] To assess the effect of soluble SorCS1 on body weight in an obese mouse model that spontaneously develops type 2 diabetes, a db / db mouse strain (BKS.Cg-m+ / +Lpr from Taconic db / BomTac). These mice lack leptin receptors, so the mice become obese and develop insulin resistance and eventually develop severe diabetes at 6-8 weeks of age. Adenoviruses expressing either hsol.SorCS1 or LacZ as a control (see Example 2) were injected to examine the effect on weight. In detail, 6-week-old db / db female mice were injected with 2E9 pfu of adenovirus vector (from ViraQuest, North Liberty, IA) with hsol.SorCS1 or LacZ as a negative control virus in the tail vein. A) In the morning 9 days after virus treatment, each mouse was transferred to a metabolic cage with the measured amount of food. After 24 hours, the mice were returned to the normal mouse cage and the food in ...

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Abstract

The present invention relates to SorCS1-like agents, including SorCS1, nucleic acid molecule encoding expression of SorCS1 and fragments thereof, as well as vectors containing said nucleic acid and to cells expressing SorCS1 and said fragments, for use in a method of reducing appetite, and / or for promoting weight loss, and / or for treating obesity, and / or for increasing metabolism, and / or for increasing thermogenesis, and / or for converting white fat into brown fat

Description

[0001] This application claims the priority of Danish Patent Application No.PA 201270191 filed on April 17, 2012. This application and all documents cited in this application are incorporated by reference in their entirety. technical field [0002] The present invention relates to methods of reducing appetite, suppressing hunger and / or treating obesity by administering SorCS1, preferably SorCS1 polypeptides and soluble fragments and variants thereof. Background technique [0003] Obesity is a medical condition in which body fat has accumulated to such an extent that it may adversely affect health. Clinically, the World Health Organization (WHO) defines obesity as a body mass index (BMI) over 30. In the obese population, three different subcategories can be defined based on the severity of obesity, class I obesity (BMI 30.0-34.9), class II obesity (BMI 35.0-39.9) and class III obesity (BMI more than 40), which is also a growing problem for public health action. It is estim...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P3/00
CPCA61K38/177A61K47/60A61K47/61A61P3/00A61P3/04C07K14/705
Inventor K-M·彼泽森A·尼克尔M·F·科尔比
Owner AARHUS UNIV
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