Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO

Papukashvili, Dimitri; Rcheulishvili, Nino; Deng, Yulin

doi:10.3390/nu12010184

Cited by 13 publications

(14 citation statements)

References 102 publications

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“…This inhibition needs to be further explored in terms of adipocyte biology, since it has already been reported that tyramine influences lipid deposition, under both in vitro and in vivo conditions [55]. Another observation linking adipose tissue physiology and PrAO activity is that methylamine and benzylamine activate glucose transport in human adipocytes in a PrAO-dependent manner [43] and that PrAO inhibitors have been proposed as anti-obesity agents [18,56].…”

Section: Discussionmentioning

confidence: 99%

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

et al. 2020

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Background: Methylxanthines including caffeine and theobromine are widely consumed compounds and were recently shown to interact with bovine copper-containing amine oxidase. To the best of our knowledge, no direct demonstration of any interplay between these phytochemicals and human primary amine oxidase (PrAO) has been reported to date. We took advantage of the coexistence of PrAO and monoamine oxidase (MAO) activities in human subcutaneous adipose tissue (hScAT) to test the interaction between several methylxanthines and these enzymes, which are involved in many key pathophysiological processes. Methods: Benzylamine, methylamine, and tyramine were used as substrates for PrAO and MAO in homogenates of subcutaneous adipose depots obtained from overweight women undergoing plastic surgery. Methylxanthines were tested as substrates or inhibitors by fluorimetric determination of hydrogen peroxide, an end-product of amine oxidation. Results: Semicarbazide-sensitive PrAO activity was inhibited by theobromine, caffeine, and isobutylmethylxanthine (IBMX) while theophylline, paraxanthine, and 7-methylxanthine had little effect. Theobromine inhibited PrAO activity by 54% at 2.5 mM. Overall, the relationship between methylxanthine structure and the degree of inhibition was similar to that seen with bovine PrAO, although higher concentrations (mM) were required for inhibition. Theobromine also inhibited oxidation of tyramine by MAO, at the limits of its solubility in a DMSO vehicle. At doses higher than 12 % v/v, DMSO impaired MAO activity. MAO was also inhibited by millimolar doses of IBMX, caffeine and by other methylxanthines to a lesser extent. Conclusions: This preclinical study extrapolates previous findings with bovine PrAO to human tissues. Given that PrAO is a potential target for anti-inflammatory drugs, it indicates that alongside phosphodiesterase inhibition and adenosine receptor antagonism, PrAO and MAO inhibition could contribute to the health benefits of methylxanthines, especially their anti-inflammatory effects.

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Section: Discussionmentioning

confidence: 99%

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

et al. 2020

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“…[ 66 ]. Thus, the scientists assumed that inhibiting SSAO activity will diminish the risks and complications in diabetes [ 38 ]. Certain natural compounds and elements discussed in this article and their impact on SSAO activity are given in Figure 2 .…”

Section: Why Is Semicarbazide-sensitive Amine Oxidase Activity Elementioning

confidence: 99%

“…SSAO inhibition may have a beneficial impact on creatine supplementation in diabetic patients. There are numbers of already well-known inhibitors capable to inhibit SSAO activity but most of them are toxic to some extent [ 38 ]. Interestingly, there are some natural compounds capable to lower increased SSAO activity.…”

Section: Introductionmentioning

confidence: 99%

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

2020

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Creatine supplementation of the population with type 2 diabetes mellitus (T2DM) combined with an exercise program is known to be a possible therapy adjuvant with hypoglycemic effects. However, excessive administration of creatine leads to the production of methylamine which is deaminated by the enzyme semicarbazide-sensitive amine oxidase (SSAO) and as a result, cytotoxic compounds are produced. SSAO activity and reaction products are increased in the serum of T2DM patients. Creatine supplementation by diabetics will further augment the activity of SSAO. The current review aims to find a feasible way to ameliorate T2DM for patients who exercise and desire to consume creatine. Several natural agents present in food which are involved in the regulation of SSAO activity directly or indirectly are reviewed. Particularly, zinc-α2-glycoprotein (ZAG), zinc (Zn), copper (Cu), histamine/histidine, caffeine, iron (Fe), and vitamin D are discussed. Inhibiting SSAO activity by natural agents might reduce the potential adverse effects of creatine metabolism in population of T2DM.

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“…Papukashvili et al [ 1 ] recently covered the enzyme semicarbazide-sensitive amine oxidase (SSAO) as a potential molecular target for the management of obesity and related diseases. While the paper is interesting, there are aspects which require clarification as it relates to caffeine.…”

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confidence: 99%

Comments to the Editor Re: Papukashvili et al. Nutrients 2020, 12, 184

Willson¹

2020

Nutrients

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Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO

Cited by 13 publications

References 102 publications

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

Methylxanthines Inhibit Primary Amine Oxidase and Monoamine Oxidase Activities of Human Adipose Tissue

Beneficial Impact of Semicarbazide-Sensitive Amine Oxidase Inhibition on the Potential Cytotoxicity of Creatine Supplementation in Type 2 Diabetes Mellitus

Comments to the Editor Re: Papukashvili et al. Nutrients 2020, 12, 184

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