Evidence map›Paper›PMID 39161060›Full record

ArticleDiabetes, obesity & metabolism2024

Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction.

JoAnne J Babula, Dinh Bui, Heather L Stevenson, Stanley J Watowich, Harshini Neelakantan

Abstract read
In one paragraph

Article in Diabetes, obesity & metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

JoAnne J BabulaRidgeline Therapeutics, Houston, Texas, USA.
Dinh BuiRidgeline Therapeutics, Houston, Texas, USA.
Heather L StevensonDepartment of Pathology, University of Texas Medical Branch at Galveston, Galveston, Texas, USA.
Stanley J WatowichRidgeline Therapeutics, Houston, Texas, USA.
Harshini NeelakantanRidgeline Therapeutics, Houston, Texas, USA.ORCID 0000-0003-2913-1824

Funding

UTMB Clinical and Translational Science AwardKL2TR001441 · NCATS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI AMEREDES, BILL T · 2015 to 2024
$4.0M
Dose-ranging safety and efficacy studies to advance novel mechanism-of-action small molecule leads to treat obesity-linked type 2 diabetesR41DK119052 · NIDDK · RIDGELINE THERAPEUTICS, LLC · PI WATOWICH, STANLEY · 2018 to 2018
$300k
Congressionally Directed Medical Research Programs PR180216Division of Diabetes, Endocrinology, and Metabolic Diseases 1R41DK119052-01NCATS NIH HHS KL2 TR001441NCATS NIH HHS KL2TR001441-06NIDDK NIH HHS R41 DK119052
6 · The paper itself

Abstract

aimTo assess the effects of a small-molecule nicotinamide N-methyltransferase (NNMT) inhibitor, 5A1MQ, on body composition, metabolic variables, fatty liver pathologies, and circulating biomarkers in diet-induced obese (DIO) mice, and characterize its plasma pharmacokinetics (PK) and tissue distribution in vivo. MATERIALS AND

methodsDIO mice were administered vehicle or 5A1MQ once daily for 28 days. Longitudinal measures of body composition, blood glucose and plasma insulin levels, and terminal measures of liver histopathology and serum markers, were evaluated. Plasma and tissue PK were established in age- and strain-matched mice after intravenous, oral, and subcutaneous dosing of 5A1MQ.

results5A1MQ treatment dose-dependently limited body weight and fat mass gains, improved oral glucose tolerance and insulin sensitivity, and suppressed hyperinsulinaemia in DIO mice. Liver histology from 5A1MQ-treated DIO mice showed attenuated hepatic steatosis and macrophage infiltration, and correspondingly reduced liver weight, size, and triglyceride levels. 5A1MQ treatment normalized circulating levels of alanine transaminase, aspartate transaminase, and ketone bodies, supporting an overall improvement in liver and metabolic functions. The pharmacodynamic effects of 5A1MQ were further corroborated by its high systemic exposure and effective distribution to metabolically active tissues, including adipose, muscle and liver, following subcutaneous dosing of mice.

conclusionsThis work validates NNMT inhibition as a viable pharmacological approach to ameliorate metabolic imbalances and improve liver pathologies that develop with obesity.

Indexed as

Nicotinamide N-MethyltransferaseObesityAnimalsBlood GlucoseBody CompositionDiet, High-FatEnzyme InhibitorsFatty LiverInsulin ResistanceLiverMaleMiceMice, Inbred C57BLMice, ObeseBlood GlucoseEnzyme InhibitorsNicotinamide N-MethyltransferaseNnmt protein, mouseanimal pharmacologyantiobesity drugdrug developmentpharmacodynamicspharmacokineticstype 2 diabetes

Identifiers

PMID39161060
PMCPMC11622326

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.