Acta Physiologica最新文献

Sodium (Na⁺) supports metabolic, neural, and muscular functions, and plays a critical role in fluid volume and blood pressure homeostasis. For many wild mammals, inadequate Na⁺ intake can lead to hyponatremia, where low Na⁺ levels disrupt fluid balance and may cause seizures or death [1]. Conversely, chronic excess in Na⁺ intake, common in both humans and domestic animals, may increase blood pressure and elevate the risk of cardiovascular disease and premature death [2]. Nevertheless, there remains considerable debate regarding the mechanisms of Na⁺ balance and why some individuals exhibit greater Na⁺ sensitivity [3].

Mammals, including humans, assimilate most (> 90%) of their dietary Na⁺ into the bloodstream [4]. Consequently, elevated Na⁺ consumption can quickly raise blood Na⁺ levels above the narrow limits required to maintain osmotic balance and blood pressure. To prevent this, mammals have evolved a number of mechanisms for regulating excess Na⁺ from the body [4]. The primary pathway is renal excretion of Na⁺ in urine [1, 3]. A secondary mechanism involves secretion of Na⁺ from the bloodstream into the large intestine for elimination in feces, though this is typically an order of magnitude smaller [4]. Third, mammals have evolved a specialized mechanism for buffering excess Na⁺ in the bloodstream: the temporary storage of Na⁺ in extrarenal body tissues [5].

The idea that mammals can store excess Na⁺ originated in the early 1900s, but more contemporary work by Titze and colleagues has shifted the paradigm regarding how the body handles excess Na [5, 6]. Traditionally, it was believed that increased Na⁺ intake required proportional increases in water to maintain extracellular osmolarity, while the kidneys excreted surplus Na⁺ to restore Na⁺ balance. However, recent evidence suggests that Na⁺ can be stored in extrarenal body tissues without commensurate water retention [5]. Most research has identified skin and muscle as the primary sites of Na storage, where Na⁺ binds to negatively charged glycosaminoglycans (GAGs) [5]. However, bone contains ~45% of total body Na, and while only one third of this Na⁺ is thought to be readily exchangeable [3], this would represent a substantial component of the body's short-term Na storage capacity. Still, the magnitude and dynamics of extrarenal Na⁺ storage remain poorly understood, with inconsistencies among species and individuals. For example, a study on dogs showed no signs of extrarenal Na⁺ storage [7], while others suggested that Na⁺ associated with GAGs remai

The July issue of Acta Physiologica contains a beautiful example of how experimental biology provides new insights into the important topic of oral reception and subsequent perception of fatty substances in mammals. In the paper “Fatty acid taste quality information via GPR40 and CD36 in the posterior tongue of mice,” Nagai and colleagues [1] skillfully performed surgical experiments, that, combined with additional behavioral tests shed new light on the circuitry of fatty acid signaling in the mouth. The paper contains observations that easily could have been missed if less attention would have been paid to details. The authors reach the tempting (and debatable) conclusion that long-chain fatty acids (LCFA), at least for mice, taste like sweet and/or umami tastants.

In an earlier paper by the same group, also published in Acta Physiologica [2], electrophysiological measurements on single chorda tympani nerve fibers coming from the anterior tongue were performed on wildtype mice and knockout mice that lack the G protein-coupled receptor GPR120, also known as free fatty acid receptor 4 (FFAR4). GPR120 is one of the proteins that have been identified about two decades ago [3, 4] to be involved in fatty acid tasting, together with other proteins, including the G protein-coupled receptor GPR40, also known as free fatty acid receptor 1 (FFAR1) and the LCFA transporter CD36 (“cluster of differentiation 36”) [see [5] for a review]. These three proteins have very diverse roles in different organs and tissues. Both GPR120 and GPR40 function in pancreatic insulin signaling, and act as the prime receptors in the gut-brain axis of fatty acid signaling that determine the long-term “wanting” of high energy nutrients like sugars and fat [6]. Those functions are but a few examples of many for GPR120 and GPR40. CD36, on the other hand, is the high affinity transporter needed to import the fuel into demanding tissues such as the cardiac muscle, a tissue that mainly relies on the mitochondrial oxidation of LCFA for energy generation. CD36 also has many other functions [3, 5].

Whether the taste of fat (by sensing of LCFA that result from oral lipase actions on triglycerides) should be considered as the sixth taste modality (next to sweet, bitter, umami, salt and sour) has long been debated, but much evidence from experimental biology pleads for it. The specific term “oleogustus” has been coined [7] to provide a word that is easily recognized as pertaining to the taste of oily or fatty substances without referring to other sensations of fat perception, like texture and viscosity. Indeed, humans are quite capable of tasting free fatty acids of different chain lengths. Short-chain fatty acids taste sour, medium-chain fatty acids are experienced as irritants, and LCFA taste differently than any of the other basic modalities. LCFA are described as unpalatable [