Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice

Abstract Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi tre...

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Autores principales:	Catherine M. Sampson, Andrea L. Dimet, Harshini Neelakantan, Kehinde O. Ogunseye, Heather L. Stevenson, Jonathan D. Hommel, Stanley J. Watowich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87f2fa77c3f847f5b4521dfa072c052a
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spelling	oai:doaj.org-article:87f2fa77c3f847f5b4521dfa072c052a2021-12-02T15:54:06ZCombined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice10.1038/s41598-021-85051-62045-2322https://doaj.org/article/87f2fa77c3f847f5b4521dfa072c052a2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-85051-6https://doaj.org/toc/2045-2322Abstract Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.Catherine M. SampsonAndrea L. DimetHarshini NeelakantanKehinde O. OgunseyeHeather L. StevensonJonathan D. HommelStanley J. WatowichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine M. Sampson Andrea L. Dimet Harshini Neelakantan Kehinde O. Ogunseye Heather L. Stevenson Jonathan D. Hommel Stanley J. Watowich Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
description	Abstract Obesity is a large and growing global health problem with few effective therapies. The present study investigated metabolic and physiological benefits of nicotinamide N-methyltransferase inhibitor (NNMTi) treatment combined with a lean diet substitution in diet-induced obese mice. NNMTi treatment combined with lean diet substitution accelerated and improved body weight and fat loss, increased whole-body lean mass to body weight ratio, reduced liver and epididymal white adipose tissue weights, decreased liver adiposity, and improved hepatic steatosis, relative to a lean diet substitution alone. Importantly, combined lean diet and NNMTi treatment normalized body composition and liver adiposity parameters to levels observed in age-matched lean diet control mice. NNMTi treatment produced a unique metabolomic signature in adipose tissue, with predominant increases in ketogenic amino acid abundance and alterations to metabolites linked to energy metabolic pathways. Taken together, NNMTi treatment’s modulation of body weight, adiposity, liver physiology, and the adipose tissue metabolome strongly support it as a promising therapeutic for obesity and obesity-driven comorbidities.
format	article
author	Catherine M. Sampson Andrea L. Dimet Harshini Neelakantan Kehinde O. Ogunseye Heather L. Stevenson Jonathan D. Hommel Stanley J. Watowich
author_facet	Catherine M. Sampson Andrea L. Dimet Harshini Neelakantan Kehinde O. Ogunseye Heather L. Stevenson Jonathan D. Hommel Stanley J. Watowich
author_sort	Catherine M. Sampson
title	Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
title_short	Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
title_full	Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
title_fullStr	Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
title_full_unstemmed	Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
title_sort	combined nicotinamide n-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/87f2fa77c3f847f5b4521dfa072c052a
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Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice

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