Trimethylaminuria

Trimethylaminuria (TMAU) or “Fish Odor Syndrome” is a disorder caused by increased concentrations of the volatile amine trimethylamine (TMA) in body fluids resulting in an unpleasant odor. The excess TMA may occur either due to deficient hepatic oxidation (primary) or increased bacterial generation (secondary). Testing urine for TMA concentration is the first line of investigation, preferably following a dietary load of a TMA precursor such as choline. Measurement of TMA and TMA-oxide are used as a guide to determine a primary or secondary cause, which can be confirmed by DNA analysis. FMO3 deficiency may have further clinical consequences due to the wide range of substrates oxidized by the enzyme including many drugs. Treatment of both primary and secondary TMAU relies on restriction of dietary precursors of TMA, antibiotic-based reduction of gut flora, and odor chelators. Riboflavin may also benefit some patients.

Drives and limits to feed intake in ruminants

The control of energy intake is complex, including mechanisms that act independently (e.g. distention, osmotic effects, fuel-sensing) as well as interacting factors that are likely to affect feeding via their effects on hepatic oxidation. Effects of ruminant diets on feed intake vary greatly because of variation in their filling effects, as well as the type and temporal absorption of fuels. Effects of nutrients on endocrine response and gene expression affect energy partitioning, which in turn affects feeding behaviour by altering clearance of fuels from the blood. Dominant mechanisms controlling feed intake change with physiological state, which is highly variable among ruminants, especially through the lactation cycle. Ruminal distention might dominate control of feed intake when ruminants consume low-energy diets or when energy requirements are high, but fuel-sensing by tissues is likely to dominate control of feed intake when fuel supply is in excess of that required. The liver is likely to be a primary sensor of energy status because it is supplied by fuels from the portal drained viscera as well as the general circulation, it metabolises a variety of fuels derived from both the diet and tissues, and a signal related to hepatic oxidation of fuels is conveyed to feeding centres in the brain by hepatic vagal afferents stimulating or inhibiting feeding, depending on its energy status. The effects of somatotropin on export of fuels by milk secretion, effects of insulin on gluconeogenesis, and both on mobilisation and repletion of tissues, determine fuel availability and feed intake over the lactation cycle. Control of feed intake by hepatic energy status, affected by oxidation of fuels, is an appealing conceptual model because it integrates effects of various fuels and physiological states on feeding behaviour.

Control of food intake by metabolism of fuels: a comparison across species

Research with laboratory species suggests that meals can be terminated by peripheral signals carried to brain feeding centres via hepatic vagal afferents, and that these signals are affected by oxidation of fuels. Pre-gastric fermentation in ruminants greatly alters fuels, allowing mechanisms conserved across species to be studied with different types and temporal absorption of fuels. These fuels include SCFA, glucose, lactate, amino acids and long-chain fatty acid (FA) isomers, all of which are absorbed and metabolised by different tissues at different rates. Propionate is produced by rumen microbes, absorbed within the timeframe of meals, and quickly cleared by the liver. Its hypophagic effects are variable, likely due to its fate; propionate is utilised for gluconeogenesis or oxidised and also stimulates oxidation of acetyl-CoA by anapleurosis. In contrast, acetate has little effect on food intake, likely because its uptake by the ruminant liver is negligible. Glucose is hypophagic in non-ruminants but not ruminants and unlike non-ruminant species, uptake of glucose by ruminant liver is negligible, consistent with the differences in hypophagic effects between them. Inhibition of FA oxidation increases food intake, whereas promotion of FA oxidation suppresses food intake. Hypophagic effects of fuel oxidation also vary with changes in metabolic state. The objective of this paper is to compare the type and utilisation of fuels and their effects on feeding across species. We believe that the hepatic oxidation theory allows insight into mechanisms controlling feeding behaviour that can be used to formulate diets to optimise energy balance in multiple species.

Antiobesity and Hypoglycaemic Effects of Aqueous Extract ofIbervillea sonoraein Mice Fed a High-Fat Diet with Fructose

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported thatIbervillea sonoraehad hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueousI. sonoraeextract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment withI. sonoraeaqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract fromI. sonoraeroot prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity.