Abstract
As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL−1 for CG, T5, and T10, respectively: p < 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p < 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism.
Highlights
Vitamin B1, known as thiamine, is an essential precursor of thiamine pyrophosphate (TPP), a universal coenzyme for decarboxylation of α-keto acids with central roles in energy metabolism in all living organisms [1,2]
Of particular importance to energy metabolism are the roles of TPP as a coenzyme for the mitochondrial α-ketoacid dehydrogenases: pyruvate dehydrogenase (PDH), branchedchain ketoacids dehydrogenase (BCKDH), and α-ketoglutarate dehydrogenase (α-KGDH)
Owing to the potential metabolic benefits of high-dose thiamine therapy, with respect to reduction of liver steatosis [18] and blood glucose in diabetes [13], we investigated its effects on body weight, blood glucose, non-esterified fatty acids (NEFA), and selected serum parameters under positive energy balance (PEB) and negative energy balance (NEB)
Summary
Vitamin B1, known as thiamine, is an essential precursor of thiamine pyrophosphate (TPP), a universal coenzyme for decarboxylation of α-keto acids with central roles in energy metabolism in all living organisms [1,2]. As a coenzyme for BCKDH, TPP has a vital role in the utilization of branched-chain amino acids, primarily from muscles, as a fuel source during starvation [6] These roles emphasize the importance of thiamine bioavailability to partial and anaerobic catabolism of glucose and amino acids. We have used a nutritional model of fatty liver in sheep [17] to show that high-dose vitamin B1 therapy prevents liverfat accumulation driven by overnutrition [18]. Whether this substantial effect of thiamine on the liver fat content extends to extrahepatic tissues, with potential implications for weight control, is unclear. To gain metabolic insight into the treatment effects, selected relevant circulating metabolites and minerals were monitored before and during the study
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