What is the clinical evidence from this study?

Study design: Other. Population: Cardiometabolic disease. Intervention: Il6 variant CC genotype vs. Il6 wild-type GG genotype. Primary outcome: Cardiomyocyte area in male mice (µm2) (p=<0.05).

What question did this study set out to answer?

The study aims to investigate how the IL6 -174 G/C variant affects cardiometabolic responses to high fat diet in mice.

March 25, 2026Open Access

An IL6 variant -174 G-C alters cardiac hypertrophy but not cardiometabolic responses to HFD in mice

Q: What are the key findings of this study?

The Il6 variant CC genotype did not alter cardiometabolic responses to a high-fat diet in mice, but decreased male cardiomyocyte area and increased female cardiomyocyte area.

Q: What question did this study set out to answer?

The study aims to investigate how the IL6 -174 G/C variant affects cardiometabolic responses to high fat diet in mice.

Key Result

The Il6 variant CC genotype did not alter cardiometabolic responses to a high-fat diet in mice, but decreased male cardiomyocyte area and increased female cardiomyocyte area.

Key Points

The study aims to investigate how the IL6 -174 G/C variant affects cardiometabolic responses to high fat diet in mice.
Utilized knock-in mice with GG wildtype or CC variant genotypes for IL6
Mice were subjected to a high fat diet to assess metabolic responses
Evaluated cardiomyocyte size differences between sexes among variant and control groups.
CC mice showcased higher systemic IL6 levels, but similar weight and energy levels as GG mice
Cardiomyocyte size varied by sex: males had smaller volume while females had larger volume but smaller heart mass compared to GG controls
The IL6 variant did not increase susceptibility to cardiometabolic disease under the tested conditions.

Structured PICO

Does the IL6 promoter variant (-174 G/C) alter cardiometabolic responses to a high-fat diet in mice?

Population

Male and female knock-in mice of a C57Bl/6 J background strain with a GG wildtype or variant CC genotype for the murine homolog of rs1800795 (Il6 variant), fed a high-fat diet (60% fat by calorie content) from 10 weeks of age.

Intervention

Variant CC genotype for the murine homolog of the IL6 promoter variant rs1800795 (-174 G/C).

Comparator

Wild-type GG genotype.

Outcome

Cardiometabolic responses to high-fat diet, including weight gain, energy expenditure, adipose tissue inflammation, glucose homeostasis, and cardiac function.surrogate

In a controlled experimental setting, the IL6 promoter variant (-174 G/C) alters cardiac hypertrophy in a sex-specific manner but does not increase susceptibility to other cardiometabolic disease features in mice fed a high-fat diet.

Main Result

Absolute Event Rate: 1061% vs 1402%

p-value: p=<0.05

Limitations

Cardiomyocyte volume was calculated using a pre-determined rendered cell volume constant derived from rat studies.
Calculation of myocyte numbers does not account for any fibrosis or apoptosis that may be present.
Limited by the 10-week duration of the high-fat diet intervention, which may not be long enough to observe cumulative structural and functional impacts.

Abstract

Chronic elevations in interleukin-6 (IL6) signaling have been shown to exacerbate features of cardiometabolic disease. A common variant in the IL6 promoter (location -174 G/C, identifier rs1800795) is associated with increased circulating IL6, and increased cardiometabolic disease incidence in some populations. This study’s objective was to isolate the impact of this gene variant on cardiometabolic responses to metabolic stress, using knock-in mice with a GG wildtype or variant CC genotype for the murine homolog of rs1800795. Male and female IL6 variant CC mice on a high fat diet exhibited enhanced systemic IL6 levels but similar weight gain, energy expenditure, adipose tissue inflammation, glucose homeostasis, and cardiac function relative to control GG mice. Sex differences in the effect of the IL6 variant on cardiomyocyte dimensions were observed, with male variant mice exhibiting smaller cardiomyocyte volume, and female variant mice exhibiting larger cardiomyocyte volume with smaller raw heart mass relative to control GG mice. These findings suggest that, in a controlled experimental setting, the IL6 promoter variant (−174 G/C) does not increase susceptibility to cardiometabolic disease. Further work is required to understand the mechanistic link between this IL6 variant and associated increased cardiometabolic risk observed in population studies.

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