This study aimed to investigate the putative role of the triglyceride-glucose index (TyG index) computed as ln[TG (mg/dl)×glucose (mg/dl)/2] and derived proxies as predictors of adiposity and weight loss changes after a low-calorie diet (LCD) intervention. A total of 744 adult participants from the multicentre DIOGenes intervention study were prescribed a LCD (800kcal/day) during 8weeks. Body composition and fat content at baseline and after 8weeks were estimated by DEXA/BIA. A multivariate analysis approach was used to estimate the difference in ΔWeight1-2 (kg), ΔBMI1-2 (kg/m2 ) or ΔFat1-2 (%) between the basal value (point 1) and after 8weeks following a LCD (point 2), respectively. The TyG index at baseline (TyG1 ), after following the LCD for 8weeks (TyG2 ) or the TyG index differences between both time points (ΔTyG1-2 ) were analysed as predictors of weight and fat changes. TyG1 was associated with ΔWeight1-2 (kg) and ΔBMI1-2 (kg/m2 ), with β=0.812 (p=.017) and β=0.265 (p=.018), respectively. Also, TyG2 values were inversely related to ΔFat1-2 (%), β=-1.473 (p=.015). Moreover, ΔTyG1-2 was associated with ΔWeight1-2 (kg) and ΔFat1-2 (%), β=0.689 (p=.045) and β=1.764 (p=.002), respectively. Furthermore, an association between TyG2 and resistance to fat loss was found (p=.015). TyG1 index is a good predictor of weight loss induced by LCD. Moreover, TyG2 was closely related to resistance to fat loss, while ΔTyG1-2 values were positively associated with body fat changes. Therefore, TyG index and derived estimations could be used as markers of individualized responses to energy restriction and a surrogate of body composition outcomes in clinical/epidemiological settings in obesity conditions.