Nutritional regulation of the anabolic fate of amino acids within the liver in mammals: concepts arising fromin vivostudies

Abstract

At the crossroad between nutrient supply and requirements, the liver plays a central role in partitioning nitrogenous nutrients among tissues. The present review examines the utilisation of amino acids (AA) within the liver in various physiopathological states in mammals and how the fates of AA are regulated. AA uptake by the liver is generally driven by the net portal appearance of AA. This coordination is lost when demands by peripheral tissues is important (rapid growth or lactation), or when certain metabolic pathways within the liver become a priority (synthesis of acute-phase proteins). Data obtained in various species have shown that oxidation of AA and export protein synthesis usually responds to nutrient supply. Gluconeogenesis from AA is less dependent on hepatic delivery and the nature of nutrients supplied, and hormones like insulin are involved in the regulatory processes. Gluconeogenesis is regulated by nutritional factors very differently between mammals (glucose absorbed from the diet is important in single-stomached animals, while in carnivores, glucose from endogenous origin is key). The underlying mechanisms explaining how the liver adapts its AA utilisation to the body requirements are complex. The highly adaptable hepatic metabolism must be capable to deal with the various nutritional/physiological challenges that mammals have to face to maintain homeostasis. Whereas the liver responds generally to nutritional parameters in various physiological states occurring throughout life, other complex signalling pathways at systemic and tissue level (hormones, cytokines, nutrients, etc.) are involved additionally in specific physiological/nutritional states to prioritise certain metabolic pathways (pathological states or when nutritional requirements are uncovered).

Altered Metabolome of Lipids and Amino Acids Species: A Source of Early Signature Biomarkers of T2DM

“…On the other hand, AA are also de novo biosynthesized from the Krebs cycle-derived carboxylic acid-intermediates by transamination. These free AA modulate the AA-type-dependent glucagon and insulin secretion and hence glucose metabolism [13]. In short, AA are not only an energy reservoir for gluconeogenesis, but their de novo biosynthesiz influences the glucagon and insulin release.…”

“…Many epidemiological cohort studies have witnessed an increased level of AA in newly diagnosed diabetic patients in the follow up investigations hinting towards an impaired glucose/hexoses metabolism [14]. An increased serum AA level reduced the insulin sensitivity and uptake of hexoses by offering competition at the substrate level to glucose oxidation and also by interfering with insulin signaling [11,13]. Higher serum AA levels were found to diminish the peripheral uptake of hexoses along with the suppression of endogenous glucose production (EGP) and body glucose disposal by 25% [15].…”

NQO1 protects obese mice through improvements in glucose and lipid metabolism

“…4. Amino acids were also included in the analysis because the liver plays a key role in endogenous glucose production through gluconeogenesis 53 . Remarkably, compared to WT, livers of HFD-fed Tg mice exhibited enhanced glucose and redox metabolism (Fig.…”

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“…Blood glucose homeostasis is maintained through a combination of the following processes: digestion of feed carbohydrates, liver glycogen metabolism and glucose synthesis from various non-carbohydrate precursors (gluconeogenesis) [15]. Poultry has a higher blood glucose level than farm animals.…”