Abstract
INTRODUCTION: The Very-Low Energy-Ketogenic Therapy: (VLEKT) is an effective therapy for obesity and metabolic dysfunction, but the factors driving variability in the treatment response remain unclear. HOMA is a well-established marker of insulin sensitivity during dietary interventions, whereas the Leptin/Adiponectin Ratio (LAR) appears as a novel indicator of adipose tissue inflammation and endocrine remodeling. METHODS: Thirty-seven adults with obesity completed an 8-week VLEKT. Anthropometry, body composition, liver status (FibroScan®), serum biochemistry, circulating adipokine and fibrogenic markers (leptin, adiponectin, resistin, chemerin, visfatin, RBP4, SHBG, FGF21, PAI-1, and follistatin) were assessed at baseline (T0) and post-intervention (T1). LAR or HOMA associations with anthropometric, hepatic, renal, and inflammatory parameters were analyzed using Spearman correlations. RESULTS: VLEKT produced significant reductions in body weight, BMI, fat mass, fasting glucose, insulin, HOMA, triglycerides, LDL, CAP, and liver stiffness. LAR decreased markedly, indicating improved adipose endocrine-inflammatory balance, while chemerin and RBP4 also declined significantly. Baseline HOMA predicted dyslipidaemia and hepatic steatosis at T1, and longitudinal changes in HOMA correlated with improvements in BMI, lipid profile, fat mass, and GGT. LAR demonstrated broader systemic associations: higher baseline LAR was linked to lower fat-free mass and impaired renal markers, whereas its reduction correlated with improved steatosis, creatinine, uric acid, and calcium homeostasis. DISCUSSION: VLEKT induced substantial metabolic and inflammatory remodeling. LAR emerged as a multidimensional biomarker reflecting adipose tissue inflammation, hepatic adaptation, and renal homeostasis, while HOMA primarily captured changes related to insulin sensitivity, lipid metabolism, and hepatic status. Their complementary profiles support combined use for personalized monitoring of VLEKT response and early identification of metabolic improvement.