2018
DOI: 10.1016/j.orcp.2017.08.003
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Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity

Abstract: Pharmacological suppression of RA synthesis via inhibition of ALDH1A1 may be a potential target for treatment of obesity.

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Cited by 29 publications
(34 citation statements)
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“… 11 , 12 Furthermore, increased production of retinoic acid by intestinal CD14 + macrophages associated with local induction of ALDH1A1 expression was shown to contribute to their inflammatory phenotype in Crohn’s disease patients. 13 These findings suggest that inhibition of ALDH1A1 enzymatic activity may offer new therapeutic options not only for cancer but also for obesity, 14 diabetes, and inflammation. As such, discovery of novel small molecule ALDH (e.g., ALDH1A1) inhibitors with suitable drug-like properties and selectivity profiles is a prudent approach for potential new cancer therapeutics and other diseases.…”
Section: Introductionmentioning
confidence: 99%
“… 11 , 12 Furthermore, increased production of retinoic acid by intestinal CD14 + macrophages associated with local induction of ALDH1A1 expression was shown to contribute to their inflammatory phenotype in Crohn’s disease patients. 13 These findings suggest that inhibition of ALDH1A1 enzymatic activity may offer new therapeutic options not only for cancer but also for obesity, 14 diabetes, and inflammation. As such, discovery of novel small molecule ALDH (e.g., ALDH1A1) inhibitors with suitable drug-like properties and selectivity profiles is a prudent approach for potential new cancer therapeutics and other diseases.…”
Section: Introductionmentioning
confidence: 99%
“…This bioinformatic result, which at first glance appears to be contradictory to the biochemical results regarding an increased glycolytic activity, can be discussed under various aspects: the gene products of the above mentioned genes, such as the alcohol dehydrogenase 1C (ADH1C) and the aldehyde dehydrogenase 1 family member A1 (ALDH1A1), are indirectly associated to glycolysis. Both gene products are involved in alcohol metabolism and the ALDH1A1 is also involved in the regulation of the metabolic response to a high-fat diet [46,47]. In a regulatory context, the protein phosphatase, Mg2+/Mn2+ dependent 1L (PPM1L) is also of interest.…”
Section: Discussionmentioning
confidence: 99%
“…Tissues were homogenized in 25 mM Tris buffer (pH 7.4) containing 0.25 M sucrose, 1 mM DTT with metal lysing matrix beads (MP Biomedicals) and centrifuged at 10,000× g for 15 min. Supernatants containing cytosolic ALDH1A enzymes (S10) were used to determine RA synthesis capacity as previously reported [ 39 ]. Briefly, S10 fractions of liver (15 µg), testis (15 µg) or MLN (30 µg) were incubated with 1 µM retinal and 2 mM NAD for 10 min at 37 °C in an enzyme activity buffer (10 mM HEPES, 150 mM KCl, 2 mM EDTA, pH 7.5).…”
Section: Methodsmentioning
confidence: 99%
“…Briefly, S10 fractions of liver (15 µg), testis (15 µg) or MLN (30 µg) were incubated with 1 µM retinal and 2 mM NAD for 10 min at 37 °C in an enzyme activity buffer (10 mM HEPES, 150 mM KCl, 2 mM EDTA, pH 7.5). Enzyme activity was quenched with acetonitrile: methanol (1:1, vol: vol) containing all- trans RA-d5 (internal standard), and supernatants (3500× g , 10 min) were collected to measure RA using LC-MS [ 39 ]. RA synthesis capacity (pmol/µg prot/min) was expressed as % of control (animals treated with vehicle).…”
Section: Methodsmentioning
confidence: 99%
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