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June 7, 2026Diabetes

APOA4 infusion reduces hepatic lipids and improves glucose tolerance in old but not young mice.

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Why the study?

Aging is associated with decreased hepatic fatty acid oxidation, impaired glucose tolerance, and reduced APOA4 levels, leading to the hypothesis that APOA4 improves age-related glucose homeostasis.

Does Apolipoprotein A4 infusion improve glucose homeostasis and reduce hepatic lipid accumulation in aging mice?

Population

Young and old male mice fed a chow diet

Comparison

APOA4 infusion at a physiological dose vs saline infusion

Design

Preclinical animal study

Follow-up

4 weeks

Key result

A 4-week infusion of APOA4 increased hepatic fatty acid oxidation, reduced liver weight and hepatic lipid accumulation, and improved glucose tolerance in old male mice, but not in young mice.

Authors

NBNosheen BashirZLZACHARY LARUSSAHSHaifei Shi

Discussion

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Overview

Hypothesis-generating for APOA4 in age-related metabolic decline; leaves open human translation.

Key Points

  • To evaluate the effects of Apolipoprotein A4 on hepatic lipid accumulation and glucose tolerance in aging.
  • Infusion of saline or APOA4 for 4 weeks in male mice
  • Assessment of hepatic fatty acid oxidation, lipid accumulation, and glucose tolerance
  • Comparison between young and old mice in response to APOA4 treatment
  • APOA4 infusion increased hepatic fatty acid oxidation in old mice, leading to reduced liver weight and lipid accumulation
  • Improved glucose tolerance was observed in old mice receiving APOA4 infusion, but not in young mice

Structured PICO

Does Apolipoprotein A4 infusion improve glucose homeostasis and reduce hepatic lipid accumulation in aging mice?

P
Population
Young and old male mice fed a chow diet.
I
Intervention
Apolipoprotein A4 (APOA4) infusion at a physiological dose for 4 weeks
C
Comparator
Saline infusion for 4 weeks
O
Outcome
Hepatic fatty acid oxidation, hepatic lipid accumulation, and glucose tolerancesurrogate

APOA4 infusion improves aging-related glucose homeostasis and reduces hepatic lipid accumulation in old mice, suggesting a potential therapeutic role in age-related metabolic decline.

Cite This Study

Bashir et al. (2026) studied Aging-related glucose homeostasis and hepatic lipid accumulation. Apolipoprotein A4 (APOA4) vs. Saline was evaluated on Hepatic fatty acid oxidation, hepatic lipid accumulation, and glucose tolerance. A 4-week infusion of APOA4 increased hepatic fatty acid oxidation, reduced liver weight and hepatic lipid accumulation, and improved glucose tolerance in old male mice, but not in young mice.

synapsesocial.com/papers/6a250bca7def13d035e1bd4chttps://doi.org/10.2337/db26-2491-p
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Also Consider

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

  1. 11646-P: Apolipoprotein A4 Improves Glucose Homeostasis through Activation of BAT Thermogenesis in Obese Mice2024
  2. 2Apolipoprotein A-I Modulates Processes Associated with Diet-Induced Nonalcoholic Fatty Liver Disease in Mice2012 · 63 citations
  3. 3Apolipoprotein A4 Elevates Sympathetic Activity and Thermogenesis in Male Mice2023 · 3 citations
  4. 4Long-term Dietary Fat Intervention Affects Retinal Health in APOE Mice2025
  5. 5Skeletal Muscle Mitochondrial Response to Diet Differs by Genotype and Sex in an Alzheimer’s Disease Mouse Model2024