Fasting Whole-Body Energy Homeostasis and Hepatic Energy Metabolism in Nondiabetic Humans with Fatty Liver

Abstract

Background. Fatty liver is believed to be sustained by a higher than normal adipose-derived NEFA flux to the liver. Also, hepatic energy metabolism may be a rate-limiting step of intrahepatic fat (IHF) accumulation. Aims. To assess whole-body energy metabolism and hepatic high-energy phosphates (HEPs) in individuals with fatty liver. Methods. We studied 22 individuals with fatty liver and 22 control individuals matched for anthropometric features by means of (1) hepatic 1H-magnetic resonance spectroscopy (MRS) to measure the IHF content, (2) hepatic 31P-MRS to assess the relative content of HEPs (phosphomonoesters, phosphodiesters, inorganic phosphorus, and ATP), and (3) indirect calorimetry to assess whole-body resting energy expenditure and substrate oxidation. Results. Patients with newly diagnosed fatty liver and controls were not different for anthropometric parameters. Based on HOMA2%-S, individuals with fatty liver were more insulin resistant than controls. Resting energy expenditure and the pattern of substrate oxidation were not different between groups. Relative content of HEPs was not different between groups; in particular, the Pi/γ-ATP ratio, the most important signals in terms of monitoring energy homeostasis, was not different even if it was associated with indirect calorimetry-derived parameters of oxidative substrate disposal. Conclusions. These data demonstrate that fasting whole-body energy metabolism and the relative content of HEPs in nondiabetic patients with fatty liver are not different than those in controls when they are matched for anthropometric features.

Early changes in hepatic energy metabolism and lipid content in recent-onset type 1 and 2 diabetes mellitus

“…As to hepatic energy metabolism, limited availability of Pi for ATP synthesis can cause a decline of hepatic ATP concentrations 38 and HC nor with hepatic γATP and Pi levels suggesting that whole-body energy metabolism is not necessarily abnormal at least during early NAFLD development, in line with previous studies 39 .…”

Changes in Alanine Aminotransferase in Adults with Severe and Complicated Obesity during a Milk-Based Meal Replacement Programme

“…The exact mechanisms driving the rise in ALT levels during the early weeks of weight loss interventions are unclear and are beyond the scope of this study. It has previously been demonstrated that during fasting, increased adipose-derived non-esteri ed fatty acid (NEFA) ux to the liver occurs, promoting intra-hepatic fat accumulation [34][35][36]. Increased intrahepatic fat, in turn, has been associated with increased generation of fatty acids within the liver via de novo lipogenesis [37].…”

Changes in alanine aminotransferase in adults with severe and complicated obesity during a milk-based meal replacement programme

“…The exact mechanisms driving the rise in ALT levels during the early weeks of weight loss interventions are unclear and are beyond the scope of this study. It has previously been demonstrated that during fasting, increased adipose-derived non-esterified fatty acid (NEFA) flux to the liver occurs, promoting intra-hepatic fat accumulation [ 34 – 36 ]. Increased intrahepatic fat, in turn, has been associated with increased generation of fatty acids within the liver via de novo lipogenesis [ 37 ].…”

“…Values are presented as Mean ± SD a Denotes variables that are not normally distributed presented as median [IQR] b Denotes variables that represent values higher than normal at the start of the programme c Denotes variables that represent values that were normal at the start of the programme The exact mechanisms driving the rise in ALT levels during the early weeks of weight loss interventions are unclear and are beyond the scope of this study. It has previously been demonstrated that during fasting, increased adipose-derived non-esterified fatty acid (NEFA) flux to the liver occurs, promoting intra-hepatic fat accumulation [34][35][36]. Increased intrahepatic fat, in turn, has been associated with increased generation of fatty acids within the liver via de novo lipogenesis [37].…”