Decreased Lipid Intermediate Levels and Lipid Oxidation Rates Despite Normal Lipolysis in Patients with Hypothyroidism

Background: Hypothyroidism decreases energy expenditure and combustion of fuels, but the reported effects on lipid metabolism and insulin sensitivity are divergent and there is a lack of studies assessing rates of lipolysis and lipid oxidation. The present study was conducted to test the hypotheses that hypothyroidism decreases lipolysis, blood concentrations of free fatty acid, lipid oxidation, and insulin sensitivity. Methods: We studied 11 hypothyroid patients (thyroid-stimulating hormone: 150 mU/L) with autoimmune thyroiditis (i) before and (ii) after 2 months of triiodothyronine-euthyroidism upon levothyroxine treatment and (iii) compared the patients to 10 healthy volunteers. Subjects underwent a 3-hour study in the basal state followed by a 3-hour euglycemic clamp study, and we used a combination of lipid blood concentrations, palmitate tracer dilution, and indirect calorimetry to assess lipid metabolism. Results: Compared to euthyroid control subjects and/or euthyroid posttreatment values hypothyroid patients were characterized by (i) 40%-50% decreased concentrations of plasma free fatty acids, palmitate, and 3-OH-butyrate (p< 0.05); (ii) >50% decreased lipid oxidation by indirect calorimetry (p< 0.001); (iii) unchanged whole-body lipolysis by palmitate dilution (all p's> 0.45); (iv) 50% increased triglyceride levels (p< 0.05); and (v) similar to 30% decreased insulin sensitivity judged by glucose infusion rate values (p 0.05). Conclusions: Our data show that hypothyroidism leads to decreased concentrations and oxidation rates of lipid intermediates and increased triglyceride concentrations in the presence of unaltered rates of lipolysis. The combination of normal lipolysis, low lipid oxidation rates, and high triglyceride concentrations is compatible with increased triglyceride synthesis.