Dietary Betaine Interacts with Very Long Chain n-3 Polyunsaturated Fatty Acids to Influence Fat Metabolism and Circulating Single Carbon Status in the Cat

SIMPLE SUMMARY: The domestic cat can metabolize and thrive on a range of intakes of different dietary polyunsaturated fatty acids (PUFA). However, changes in the intake of PUFA have relatively unknown effects on concentrations of other fatty acids and metabolites. Similarly, the effect of increasing dietary betaine (which is a single carbon donor) on circulating concentrations of metabolites and fatty acids is relatively unreported. As might be expected, increasing intake of specific dietary fatty acids resulted in an increased concentration of that fatty acid and moieties containing that fatty acid. Dietary betaine increased concentration of many compounds associated with single carbon metabolism (e.g., dimethyl glycine, sarcosine, methionine) and many PUFA such as the n-6 PUFA linoleic acid (LA) and arachidonic acid (ARA) and the n-3 fatty acids α-linolenic acid (αLA), and docosahexaenoic acid (DHA). Dietary betaine interacted with the addition of dietary fish oil to dampen diet-induced increase of ARA while potentiating the increase of circulating DHA occurring with increased DHA dietary intake. Dietary betaine and fish oil also combined to reduce the circulating concentration of the renal toxin 3-indoxyl sulfate, suggesting a positive effect on the gut microbiota. These data suggest a positive effect of a daily betaine intake which exceeds 60 mg per kg body weight. The data also support an added benefit of a combined EPA+DHA daily intake of greater than 26 mg/kg body weight as well as a daily intake of 75 mg/kg body weight of alpha linolenic acid. ABSTRACT: Six foods were used to evaluate the interaction of dietary betaine and n-3 PUFA in the cat. There was no ingredient added to the control food to specifically increase betaine or n-3 fatty acids. The experimental design was a 3 × 2 factorial (fatty acids were varied from the control food which had no added source of n-3 fatty acids, flax was included as a source of 18 carbon n-3, or menhaden fish oil as a source of EPA and DHA). Foods were then formulated using these three foods as a base with added betaine or without added betaine. Forty eight cats were used in this study. Equal numbers of cats were allotted by age and gender to each of the six dietary treatments. The cats were offered food amounts to maintain weight and consumed the food to which they were assigned for the length of the study (60 days). Metabolomics, selected circulating analytes and fatty acids were analyzed at the beginning and end of the feeding period. There was an increase in single carbon metabolites (betaine, dimethyl glycine, and methionine) with the consumption of dietary betaine. Betaine also increased the concentration of specific PUFA (ARA, αLA, DHA, and the sum of all circulating PUFA). The combination of dietary betaine and fish oil resulted in a reduction of circulating 3-indoxyl sulfate which suggests a renal benefit from their combined dietary presence.