What is the clinical evidence from this study?

Study design: Other. Population: Obesity-induced vascular remodeling (n=121). Intervention: High-fat diet vs. Chow diet. Primary outcome: PDXL+ blood vessel area% in the liver.

What question did this study set out to answer?

This study aims to analyze the effects of high-fat diet feeding on the vascular structure in various non-adipose organs of male mice.

May 10, 2026Communications Biology0 citationsOpen Access

High-fat diet feeding induces organ-specific vascular remodeling with distinct temporal dynamics in male mice

EPEmmi PakarinenUniversity of Helsinki SPSatu PaavonsaloUniversity of Helsinki MLMadeleine H. LackmanUniversity of Helsinki

Key Result

High-fat diet feeding for 10 weeks decreased the podocalyxin-positive blood vessel area in the liver by 16.9% compared to chow-fed mice.

Key Points

This study aims to analyze the effects of high-fat diet feeding on the vascular structure in various non-adipose organs of male mice.
Male mice were subjected to short-term (5 days and 5 weeks) and long-term (10 weeks) high-fat diet feeding, followed by a weight loss phase of 5 weeks.
Vessel-covered area and endothelial cell numbers were assessed in seven organs: liver, heart, intestine, kidney, lung, ear skin, and retina.
HFD feeding resulted in morphological changes in the liver, heart, kidney, and intestinal vasculatures.
A negative correlation was found between body weight and vessel density in most analyzed tissues.
Changes in vessel area did not always align with alterations in endothelial cell counts.

PICO

Population

Obesity-induced vascular remodeling (n=121)

Intervention / Comparator

High-fat diet vs Chow diet (60% calories from fat)

Primary Outcome

PDXL+ blood vessel area% in the liver

Main Result

Absolute Event Rate: 6.9% vs 8.3%

Limitations

Variation between mouse weights, especially in the long-term cohorts
Use of two different chow diets created a potential confounder
Inability to quantify endothelial cell numbers and percentages across all tissues
Did not analyze parenchymal cell numbers or additional vessel parameters like branching and diameter
Blood vessel perfusion measured by lectin labeling could only be analyzed in two tissues
Only male mice were used, excluding potential sex-specific differences
The diet-induced obesity model may not fully capture the multifactorial nature of human obesity

Abstract

Abstract Obesity-induced changes in adipose vasculature are well documented, but systematic analyses in other tissues have not been as extensive. Here, we analyze the vessel-covered area and endothelial cell (EC) numbers in seven non-adipose organs (liver, heart, intestine, kidney, lung, ear skin, retina) in male mice after short-term high-fat diet (HFD) feeding (5 days or 5 weeks), long-term HFD feeding (10 weeks), and weight loss (5 weeks of HFD followed by 5 weeks of chow feeding). We show HFD-induced morphological changes in the liver, heart, kidney, and intestinal vasculatures, and a negative correlation between body weight and vessel density in most of the analyzed tissues. Interestingly, changes in vessel area do not always reflect alterations in EC numbers. Additionally, both the intestine and ear skin show preserved vessel perfusion in response to obesity. This study provides a comprehensive analysis of how different HFD feeding durations affect organotypic vasculature and reports that HFD feeding induces organ-specific vascular remodeling with distinct temporal dynamics in mice.

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