Diet-based weight-loss intervention is not associated with a meaningful change in lean soft tissue

An emerging concern is that weight-loss interventions can lead to disproportionate muscle loss. Few studies accurately quantify changes in lean soft tissue (LST) after weight loss or investigate associated molecular signatures.

The objectives of this study were to quantify LST change after a diet-based weight-loss intervention and identify protein biomarkers associated with LST retention.

Using the Diet Intervention Examining The Factors Interacting with Treatment Success cohort, we analyzed LST from dual-energy X-ray absorptiometry in three ways: 1) by body region (appendicular and total body), 2) after removing bias from fat-free adipose tissue (FFAT), and 3) relative to body size (percentage predicted LST). We also assessed 242 proteins measured in Olink Cardiovascular II, III, and Inflammation panels as predictors of LST change.

A total of 374 participants (61% female; mean age ± standard deviation (SD): 39.4 ± 6.7 y; mean body mass index ± SD: 32.3 ± 3.2 kg/m²) who had been randomly assigned to healthy low-fat or low-carbohydrate diets were pooled and analyzed at baseline and 6 mo. Total mass changed by -5.9 kg (95% confidence interval [CI]: -6.51, -5.29) in females and -7.18 kg (95% CI: -8.2, -6.16) in males. Appendicular LST change was modest at -0.80 kg (95% CI: -0.92, -0.69) in females and -1.02 kg (95% CI: -1.22, -0.83) in males. Appendicular LST losses comprised <10% of total mass loss after adjusting for FFAT. Appendicular LST relative to body size also increased at 6 mo (P < 0.001). Changes in 10 proteins in females and 27 in males predicted LST change (5% false discovery rate), with protein delta homolog 1 (DLK1)-an inhibitor of adipogenesis-as the top predictor.

Change in appendicular LST, a surrogate for skeletal muscle, was modest after 6 mo of diet-based weight loss. DLK1, an inhibitor of adipogenesis, emerged as the top protein biomarker linked to LST retention. This trial was registered at clinicaltrials.gov as NCT01826591.