Metabolic Effects of Vitamin B1 Therapy under Overnutrition and Undernutrition Conditions in Sheep.

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.

High-dose vitamin B1 therapy prevents the development of experimental fatty liver driven by overnutrition.

Fatty liver is an abnormal metabolic condition of excess intrahepatic fat. This condition, referred to as hepatic steatosis, is tightly associated with chronic liver disease and systemic metabolic morbidity. The most prevalent form in humans, i.e. non-alcoholic fatty liver, generally develops due to overnutrition and sedentary lifestyle, and has as yet no approved drug therapy. Previously, we have developed a relevant large-animal model in which overnourished sheep raised on a high-calorie carbohydrate-rich diet develop hyperglycemia, hyperinsulinemia, insulin resistance, and hepatic steatosis. Here, we tested the hypothesis that treatment with thiamine (vitamin B1) can counter the development of hepatic steatosis driven by overnutrition. Remarkably, the thiamine-treated animals presented with completely normal levels of intrahepatic fat, despite consuming the same amount of liver-fattening diet. Thiamine treatment also decreased hyperglycemia and increased the glycogen content of the liver, but it did not improve insulin sensitivity, suggesting that steatosis can be addressed independently of targeting insulin resistance. Thiamine increased the catalytic capacity for hepatic oxidation of carbohydrates and fatty acids. However, at gene-expression levels, more-pronounced effects were observed on lipid-droplet formation and lipidation of very-low-density lipoprotein, suggesting that thiamine affects lipid metabolism not only through its known classic coenzyme roles. This discovery of the potent anti-steatotic effect of thiamine may prove clinically useful in managing fatty liver-related disorders.This article has an associated First Person interview with the joint first authors of the paper.

Effect of supplementation of unprotected or protected arginine to prolific ewes on maternal amino acids profile, lamb survival at birth, and pre- and post-weaning lamb growth.

This research determined the effects of dietary supplementation with rumen-protected arginine (Pro-Arg) on metabolites and amino acids in maternal plasma and lamb survival rate at birth (LSRAB) in prolific Afec-Assaf ewes. The hypothesis was that Pro-Arg, the precursor for nitric oxide and polyamines, would increase placental development and vascularity, uteroplacental blood flow, and nutrient transport and reduce oxidative stress to increase LSRAB. Ewes were fed either their basal diet, basal diet with Pro-Arg, or basal diet with unprotected arginine (Unp-Arg; 18 g/head/d). The supplemental arginine was about 1% of the dry matter intake from day 40 or 60 of gestation until parturition. Ninety-two of 98 ewes produced live lambs. Ewes fed Pro-Arg had greater (P = 0.002) concentrations of arginine and other amino acids in plasma, whereas Unp-Arg did not affect concentrations of arginine, but decreased (P < 0.05) concentrations of some amino acids. There was no effect of treatments on gestation length (144 ± 2 d), prolificacy (2.65 lambs born per ewe), LSRAB (0.80), body weight (88.8 ± 10.8 kg), and body condition score (2.8 ± 0.6) of ewes, or birth weight and crown-rump length of lambs. The GI (BW/CRL1.5) was affected by sex of lamb (P = 0.008), parity of ewe (P = 0.002), litter size (P = 0.0001), and lamb status (P = 0.003). Of 229 lambs born, 32 were dead and 16 died before 5 mo of age, leaving 181 lambs with records on weights at birth and 5 mo of age. Interestingly, lambs born to ewes fed the Unp-Arg and Pro-Arg weighed 3.6 kg less at postnatal day 150 than lambs from control ewes.