Abstract
Background
A healthy low-fat (HLF) and healthy low-carbohydrate (HLC) diet are common strategies for weight loss that vary in their effects on adiposity and metabolism. Visceral adipose tissue (VAT) is the major contributor to metabolism deregulation, beyond subcutaneous adipose tissue (SAT). Despite strong biological evidence that a HLC diet preferentially decreases VAT, the difficulty measuring it has impeded diet trials. We estimated VAT and SAT in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) weight loss trial to compare the effects of HLF and HLC diets and effect modification by sex and insulin resistance.
Methods
In a 1-year weight loss trial, DIETFITS, we compared VAT loss between HLF and HLC diets by randomizing N = 609 adults to either diet. VAT was estimated using dual-energy x-ray absorptiometry at baseline, 6 months, and 12 months. Linear mixed models analyzed associations between diet and VAT. We built separate models to evaluate effect modification by sex and insulin resistance.
Results
Among 449 participants (60% women; mean age 39 years), VAT loss was significantly greater for those eating the HLC diet compared to the HLF diet at 6 months [10.6 cm2; 95% confidence interval (CI): 5,16.2] and 12 months (6.3 cm2; 95% CI: 0.6,12). VAT relative to SAT loss estimates were greater in the HLC diet at 6 months only. Men experienced greater HLC diet-induced VAT loss than did women. Insulin secretion status did not modify VAT loss.
Conclusions
The HLC diet was associated with greater VAT loss compared to the HLF diet over 12 months. The loss of metabolically harmful VAT was independent from SAT over 6 months. Direct estimation of adipose sub-types provides strong evidence that insulin resistance does not modulate diet response. Sex differences should be considered in effective dietary interventions targeting VAT reduction and metabolic health.
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Data availability
The data that support the findings of this study are available from the senior author, CDG, upon reasonable request.
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Acknowledgements
The authors would like to acknowledge the Gardner research team from the parent DIETFITS study. We thank Kyla Kent and Vincent Busque, who contributed to the re-analysis of the DXA scans and Christopher Dant for his editorial review. We also thank the study participants for contributing their time and effort to this study. This research was supported by grant K99HL169908 (Follis) from the National Heart, Lung, and Blood Institute.
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SF and CDG contributed to the conception; acquisition, analysis, interpretation, drafting; KMC contributed to the analysis, interpretation, drafting; MJL, MLS, and CPW contributed to the interpretation and drafting.
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Follis, S., Landry, M.J., Cunanan, K.M. et al. Effect of low-carbohydrate vs low-fat diet intervention on visceral fat estimated from dual energy X-ray absorptiometry in a 12-month randomized controlled trial. Int J Obes (2025). https://doi.org/10.1038/s41366-025-01989-x
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DOI: https://doi.org/10.1038/s41366-025-01989-x


