Methods of modulating nkx6.3

A technology of reagents and uses, applied in the field of regulating NKX6.3, can solve problems that people know little about

Pending Publication Date: 2020-12-15
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] However, little is known about whether these changes in gene expression levels are causally related to obesity and weight loss, or whether they are simply a reflection of obesity status and weight loss interventions

Method used

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  • Methods of modulating nkx6.3
  • Methods of modulating nkx6.3
  • Methods of modulating nkx6.3

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0223] Example 1: Association between NKX6.3 genetic variants and weight loss

[0224] The study involved a genetic association performed on the Diogenes weight loss intervention data and the Canadian Optifast900 study.

[0225] The Diogenes Study is a pan-European, randomized and controlled dietary intervention study that investigated the effect of dietary protein and glycemic index on weight loss and weight maintenance in obese and overweight households in eight European centers (Larsen et al. (2009) Obesity Rev. 11:76-91). Briefly, the Diogenes study included overweight / obese individuals following an 8-week low-calorie diet (LCD). LCD provides 800kcal per day by using meal replacement products (Modifast, Nutrition et Santé France).

[0226] The Canadian Optifast900 study consisted of patients enrolled in a weight management clinic who had completed a 6- to 12-week meal replacement regimen consisting of the Canadian-exclusive product Optifast900 (Nestlé Health Science, S...

Embodiment 2

[0230] Example 2: Prioritization of NKX6.3 genetic variants

[0231] Prioritization of GWA signals using a Bayesian framework to model the joint likelihood of associated p-values ​​with large-scale epigenome annotations. Such risk variance inference was performed using the RiVIERA-β framework (Li, Y. & Kellis, M. Nucleic Acids Res. 44, e144 (2016)) with 450 epigenome annotations (including histone marks, DNase I sensitivity, transcription factor binding, and localization within exons). The goal of the framework is to infer a posterior probability of disease for each input SNP, given its association p-value and overlap in functional annotation. Epigenome annotations were retrieved from Pickrell et al. (Am. J. Hum. Genet. 94, 559–573 (2014)).

[0232] The benefit of such modeling is to determine which variants are likely to be the most plausible in terms of causal / modulatory effects, even if these variants are not necessarily the most associated variants (ie, have the most e...

Embodiment 3

[0233] Example 3: In vivo function of NKX6.3

[0234] fly race : Fly stocks were maintained on a standard diet with agar, sugar, and yeast and were raised on a 12 / 12 day-night cycle in a 25°C incubator. Actin-Gal4 from Bloomington, and w1118 and UAS-HGTX IR From VDRC.

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Abstract

An agent capable of decreasing the activity of NKX6.3 for use in (i) reducing fat accumulation and / or (ii) preserving or increasing fat free mass in a subject. A method for predicting the degree of reduction in fat accumulation by applying one or more dietary interventions to a subject and / or predicting the degree of preservation or increase in fat free mass by applying one or more dietary interventions is also provided.

Description

technical field [0001] The present invention relates to agents capable of modulating the activity of NKX6.3 and the use of such agents in therapy, especially in (i) reducing fat accumulation and / or (ii) maintaining or increasing lean body mass in an individual. The invention also relates to methods of identifying such agents. Background technique [0002] Obesity is a chronic metabolic disorder that has reached epidemic proportions in many parts of the world. Obesity is a major risk factor for serious comorbidities such as type 2 diabetes, cardiovascular disease, dyslipidemia and certain types of cancer (World Health Organ. Tech. Rep. Ser. (2000) 894: i-xii, 1-253 ). [0003] Obesity refers to a condition in which an individual's body weight exceeds normal due to excessive accumulation of energy from carbohydrates, fats, etc. Extra body weight is usually retained under the skin or around internal organs in the form of fat. [0004] Empirical data indicate that a weight l...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/11A61K31/7088
CPCA61K31/7105A61K31/713C12N15/111A61P3/04A61P3/06C12N15/113C12N2310/14C12Q1/6876C12Q2600/136C12Q2600/158
Inventor A·瓦尔塞西亚J·哈格尔N·格尔多夫
Owner SOC DES PROD NESTLE SA
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