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June 7, 2026Diabetes

Microbiota depletion with antibiotics negates cardiac Akt1 metabolic benefits, resulting in ~7% higher body fat.

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Why the study?

Although cardiac mitochondrial Akt1 activation modulates metabolic homeostasis, the underlying mechanism is incompletely understood, prompting investigation into whether gut microbiota mediates these benefits.

Does gut microbiota depletion with broad-spectrum antibiotics negate the metabolic benefits of cardiac mitochondrial Akt1 activation in a mouse model of diet-induced diabetic cardiomyopathy?

Population

Inducible myocardium-specific transgenic mice (CAMCAKT) fed a high fat-high fructose diet

Comparison

Antibiotic-treated CAMCAKT mice vs untreated CAMCAKT mice and non-induced controls

Design

Transgenic animal study

Follow-up

2 months

Key result

Microbiota depletion with antibiotics negated the metabolic benefits of cardiac mitochondrial Akt1 activation, resulting in 7% higher body fat mass compared to controls.

Authors

APAdrija PathakATALBERT TARJROBERT JENQ

Discussion

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Member takes

Overview

No practice change warranted from this animal model; leaves open microbiota mediation of cardiac Akt1 metabolic effects in diabetic cardiomyopathy.

Key Points

  • This research aims to determine if gut microbiota mediates the metabolic benefits from cardiac mitochondrial Akt1 activation.
  • Used inducible myocardium-specific transgenic mouse model with activated Akt1.
  • Administered broad-spectrum antibiotics to some mice during high fat-high fructose diet feeding.
  • Compared body fat and liver composition between treated and control mice.
  • Antibiotic-treated CAMCAKT mice had 7% higher body fat mass compared to controls after 2 months on diet.
  • Untreated CAMCAKT mice showed an 8% lower body fat mass compared to controls.
  • Gut microbiota depletion reversed the metabolic benefits including improvements in fatty liver and body composition.

Structured PICO

Does gut microbiota depletion with broad-spectrum antibiotics negate the metabolic benefits of cardiac mitochondrial Akt1 activation in a mouse model of diet-induced diabetic cardiomyopathy?

P
Population
Inducible myocardium-specific transgenic mouse model (CAMCAKT) fed a high fat-high fructose diet for 2 months to assess the role of gut microbiota.
I
Intervention
Broad-spectrum antibiotics (Ampicillin and Enrofloxacin) to deplete gut microbiota
C
Comparator
Non-induced vehicle injected CAMCAKT mice (controls) and untreated CAMCAKT mice
O
Outcome
Body fat mass, serum free fatty acid levels, and hepatic steatosissurrogate

Gut microbiota depletion negates the metabolic and hepatoprotective benefits of cardiac mitochondrial Akt1 activation in a mouse model of diet-induced diabetic cardiomyopathy.

Cite This Study

Pathak et al. (2026) studied Diet-Induced Diabetic Cardiomyopathy. Broad-spectrum antibiotics (Ampicillin and Enrofloxacin) vs. Untreated CAMCAKT mice and non-induced vehicle injected controls was evaluated on Body fat mass. Microbiota depletion with antibiotics negated the metabolic benefits of cardiac mitochondrial Akt1 activation, resulting in 7% higher body fat mass compared to controls.

synapsesocial.com/papers/6a250ac07def13d035e1ace8https://doi.org/10.2337/db26-2535-p
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Abstract Fri110: Renal Tubular Mitochondrial AKT1 Improves Cardiac Function in Cardiovascular-Kidney-Metabolic Syndrome2025
  2. 22042-LB: The Gut–Fat Cross Talk in Metabolic Regulation through Microbiome2024
  3. 3High-fat diet-induced gut microbiota functional reprogramming is associated with metabolic inflammation and cardiac remodeling through the gut-heart axis in mice2026
  4. 4Gut Microbiota‐Derived Metabolites Orchestrate Metabolic Reprogramming in Diabetic Cardiomyopathy: Mechanisms and Therapeutic Frontiers2025 · 19 citations
  5. 5Dietary Nutrients, Gut Microbiota, and Cardiac Function: From Metabolic Mechanisms to Clinical Applications2026 · 7 citations