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Compositions and methods for regulating body weight and metabolic syndromes

A composition and weight-based technology, applied in the direction of biochemical equipment and methods, metabolic diseases, drug combinations, etc., can solve problems such as insulin sensitivity that does not show weight loss

Pending Publication Date: 2019-08-27
PURDUE RES FOUND INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, none of these publications demonstrate that administration of ACAT inhibitors is associated with suppression of food intake and its associated weight loss and insulin sensitivity

Method used

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  • Compositions and methods for regulating body weight and metabolic syndromes
  • Compositions and methods for regulating body weight and metabolic syndromes
  • Compositions and methods for regulating body weight and metabolic syndromes

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0173] Example 1: ACAT1 expression is positively associated with adipogenesis and obesity

[0174] To examine the function of ACAT in obesity, the expression patterns of ACAT1 and ACAT2 genes and their gene products during in vitro adipogenesis in mouse 3T3-L1 preadipocytes were examined. It was judged by real-time PCR that the level of ACAT1 mRNA in adipocytes was significantly increased 2 days after the initiation of adipogenesis (ie D2) ( figure 1 ). However, ACAT2 mRNA levels were similar between preadipocytes (D0) and mature adipocytes (D6), while a temporary decrease in ACAT2 levels was observed at D2 ( figure 1 ). Furthermore, white adipose tissue (WAT) isolated from high-fat diet-induced obese mice showed elevated mRNA levels of ACAT1 and decreased mRNA levels of ACAT2 when compared to levels in lean mice as judged by real-time PCR assays . Leptin levels were measured in WAT from lean and obese mice to confirm the development of obesity ( figure 2 ). Furthermo...

example 2

[0175] Example 2: Inhibition of Lipid Accumulation in Adipocytes by ACAT Inhibitors (Avasimibe and CI-976)

[0176] To determine the effect of ACAT inhibitors on lipid accumulation in adipocytes, mouse 3T3-L1 preadipocytes were differentiated into mature fat cells. Avasimibe solutions were prepared by dissolving in dimethylsulfoxide (DMSO). On day 6, preadipocytes and avasimibe-treated differentiated adipocytes were stained with Oil Red O to visualize accumulated intracellular lipids. Then, Oil Red O-stained lipids were extracted for spectroscopic quantification of lipids. Intracellular lipids were reduced by up to 60% in a dose-dependent manner ( Figure 3A and Figure 3B ). Avasimibe's inhibition of lipid accumulation ( Figure 4 ). Similar to avasimibe, treatment of differentiated adipocytes with the non-selective ACAT inhibitor CI-976 at a concentration range of 0 μM, 5 μM, 15 μM, and 20 μM for 6 days also resulted in a reduction in lipid accumulation, as measured...

example 3

[0178] Example 3: Avasimibe reduces adipocytes by modulating SREBP1 expression and function on lipid synthesis lipid accumulation

[0179] Because SREBP1 plays a key role in de novo fatty acid and TG synthesis, and Image 6 The data in showed a potential inhibitory effect of avasimibe on the repression of SREBP1 downstream genes involved in fatty acid and TG synthesis, so the ability of avasimibe treatment to alter SREBP1 protein expression and de novo fatty acid synthesis in adipocytes was examined. Avasimibe treatment resulted in increased levels of the 125 kDa inactive precursor form of SREBP1 in adipocytes, as judged by Western blot analysis using β-actin (protein loading control) and an SREBP1-specific antibody ( Figure 7 ).

[0180] Using deuterium-labeled glucose-d7, the effect of avasimibe on de novo fatty acid synthesis in adipocytes treated with or without avasimibe was examined. Glucose-d7-incorporated fatty acids were visualized by stimulated Raman scatterin...

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Abstract

A composition comprising an active agent that inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) is provided. With the composition, food intake can be suppressed, and / or body weight can be reduced, and / or metabolic disorders can be prevented and / or treated.

Description

[0001] cross reference [0002] This application claims the benefit of US Provisional Application 62 / 422,722, filed November 16, 2016. The disclosure thereof is expressly incorporated herein in its entirety. technical field [0003] The present invention relates to methods and compositions for inhibiting food intake, inhibiting body weight; and treating or preventing metabolic diseases. Background technique [0004] Obesity is an increasingly prevalent disease that has been shown to contribute to a variety of life-threatening medical conditions. Such medical conditions include cardiovascular disease and metabolic disease. Current efforts to treat obesity-related diseases focus on the development of drugs or inhibitors of enzymes, transcription factors and / or signaling proteins involved in neutral lipid (triglyceride) synthesis. However, given that the prevalence of obesity is still increasing, especially in the United States, there remains an important need for the identi...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61P3/06C12N9/10
CPCA61K45/06A61K31/167A61K31/18A61P3/06C12N9/1029C12Y203/01009A61P3/04A61P3/10A61K2300/00C12N15/1137C12N2310/14A61K31/7105A61K48/00C12N2310/531
Inventor 金基洪朱玉燕
Owner PURDUE RES FOUND INC
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