mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Improvement of glucose homeostasis during leptin treatment does not alter the
intestinal microbiome in male diabetic UC Davis type-2 diabetes mellitus rats.
Authors Martínez-Ruiz M, Tabor-Simecka L, Graham JL, Randolph C, Fox R, Lan R, Pack L,
LeRoith T, Stanhope KL, Yeruva L, Havel PJ, Piccolo BD
Submitted By Submitted Externally on 5/7/2026
Status Published
Journal American journal of physiology. Gastrointestinal and liver physiology
Year 2026
Date Published 5/1/2026
Volume : Pages 330 : G549 - G564
PubMed Reference 41875058
Abstract Gut dysbiosis contributes to type 2 diabetes mellitus (T2DM) progression
according to the preclinical evidence. Alterations in gut microbiome, energy
metabolism, and barrier function were observed in individuals with obesity and
insulin resistance. However, it remains unclear whether therapeutic
interventions can reverse these alterations. This study aimed to evaluate
whether improvements of glucose homeostasis resulting from leptin administration
can lead to changes in colonic epithelial metabolism and barrier function in
male UC Davis type 2 diabetic mellitus (UCD-T2DM) rats. Male UCD-T2DM rats (age:
173?±?41 days) with 6 wk postonset of diabetes were randomized to receive daily
subcutaneous injections of either phosphate buffer solution (control; n = 12) or
recombinant leptin (0.5 mg/kg; n = 12) for 4 wk. Metabolic and intestinal
outcomes were assessed, including glucose tolerance, insulin sensitivity,
glucagon-like protein 1 levels, gut permeability, microbiota composition,
short-chain fatty acids content, colon epithelial hypoxia, intestinal
morphology, and gene/protein expression. Leptin treatment significantly reduced
food intake and improved glucose homeostasis and insulin sensitivity without
affecting body weight. No changes were observed in microbiome composition, gut
permeability, or colon epithelial hypoxic gradients. Ileal villus height was
decreased, whereas colonic crypt depth was not different between leptin-treated
rats and control rats. Butyric, isocaproic, and valeric acids levels were
increased in colonic content, colonic gene expression of Pparg and Ldha was
downregulated, whereas PHD2 and Occludin protein levels were upregulated in
leptin-treated compared with control. Despite improvements of glucose
homeostasis, chronic leptin treatment did not modify gut microbiota or barrier
function markers and colonic metabolic gene expression showed no clear adaptive
shift.NEW & NOTEWORTHY Our data indicate that chronic administration of
recombinant leptin in diabetic UCD-T2DM rats does not change the gut microbiome,
despite improvements in food intake, glucose homeostasis, and insulin
sensitivity.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.