Metabolic flux analysis of branched-chain amino and keto acids (BCAA, BCKA) and β-hydroxy β-methylbutyric acid across multiple organs in the pig.

Branched-chain amino acids (BCAA) and their metabolites the branched-chain keto acids (BCKA) and β-hydroxy β-methylbutyric acid (HMB) are involved in the regulation of key signaling pathways in the anabolic response to a meal. However, their (inter)organ kinetics remain unclear. Therefore, branched-chain amino acids (BCAA) [leucine (Leu), valine (Val), isoleucine (Ile)], BCKA [α-ketoisocaproic acid (KIC), 3-methyl-2-oxovaleric acid (KMV), 2-oxoisovalerate (KIV)], and HMB across organ net fluxes were measured.

Natural helix 9 mutants of PPARγ differently affect its transcriptional activity.

Objective: The nuclear receptor PPARγ is the master regulator of adipocyte differentiation, distribution, and function. In addition, PPARγ induces terminal differentiation of several epithelial cell lineages, including colon epithelia. Loss-of-function mutations in PPARG result in familial partial lipodystrophy subtype 3 (FPDL3), a rare condition characterized by aberrant adipose tissue distribution and severe metabolic complications, including diabetes.

Transhepatic bile acid kinetics in pigs and humans.

Background & Aims: Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail.

Assessment of plasma acylcarnitines before and after weight loss in obese subjects.

Acylcarnitines, fatty acid oxidation (FAO) intermediates, have been implicated in diet-induced insulin resistance and type 2 diabetes mellitus, as increased levels are found in obese insulin resistant humans. Moreover plasma acylcarnitines have been associated with clinical parameters related to glucose metabolism, such as fasting glucose levels and HbA1c. We hypothesized that plasma acylcarnitines would correlate with energy expenditure, insulin sensitivity and other clinical parameters before and during a weight loss intervention.

The impact of altered carnitine availability on acylcarnitine metabolism, energy expenditure and glucose tolerance in diet-induced obese mice.

Aim: Acylcarnitines are fatty acid oxidation (FAO) intermediates, which have been implicated in diet-induced insulin resistance. Elevated acylcarnitine levels are found in obese, insulin resistant humans and rodents, and coincide with lower free carnitine. We hypothesized that increasing free carnitine levels by administration of the carnitine precursor γ-butyrobetaine (γBB) could facilitate FAO, thereby improving insulin sensitivity.

Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism.

Acylcarnitines are derived from mitochondrial acyl-CoA metabolism and have been associated with diet-induced insulin resistance. However, plasma acylcarnitine profiles have been shown to poorly reflect whole body acylcarnitine metabolism. We aimed to clarify the individual role of different organ compartments in whole body acylcarnitine metabolism in a fasted and postprandial state in a porcine transorgan arteriovenous model.

Plasma acylcarnitines inadequately reflect tissue acylcarnitine metabolism.

Acylcarnitines have been linked to obesity-induced insulin resistance. However the majority of these studies have focused on acylcarnitines in plasma. It is currently unclear to what extent plasma levels of acylcarnitines reflect tissue acylcarnitine metabolism.

Adaptive reciprocity of lipid and glucose metabolism in human short-term starvation.

The human organism has tools to cope with metabolic challenges like starvation that are crucial for survival. Lipolysis, lipid oxidation, ketone body synthesis, tailored endogenous glucose production and uptake, and decreased glucose oxidation serve to protect against excessive erosion of protein mass, which is the predominant supplier of carbon chains for synthesis of newly formed glucose. The starvation response shows that the adaptation to energy deficit is very effective and coordinated with different adaptations in different organs.