Dietary fatty acid oxidation is decreased in non‐alcoholic fatty liver disease: A palmitate breath test study

Abstract

Background & Aim Hepatic fat excess in non‐alcoholic fatty liver disease (NAFLD) reflects an imbalance between fat accumulation and disposal. Conflicting data exist for the role of fatty acid oxidation (FAO), one of the disposal pathways, and have mostly come from the studies delivering fatty acids (FAs) intravenously. Whether FAO of orally provided FAs is affected in NAFLD is unknown. Methods We performed a breath test study to measure FAO in subjects with NAFLD and healthy controls. Subjects ingested [1‐13C] palmitic acid (PA, 10 mg/kg) in a liquid meal and the rate of 13CO2 appearance in expired air was measured over 6 hours by a BreathID device (Exalenz) to obtain the cumulative percent dose recovered (CPDR), the total amount of ingested 13C recovered. CPDR was corrected by the results of a [1‐13C] acetate breath test, performed 1‐4 weeks later, to calculate the rate of PA β‐oxidation. Results Palmitic acid oxidation was 27% lower in 43 subjects with NAFLD compared to 11 controls (CPDR 9.5 ± 2.4% vs 13.1 ± 3.7%, P = .0001) and this persisted after correcting for acetate (29.3 ± 10.5 vs 36.6 ± 13.9, P = .03). The decrease in FAO was not because of the delayed transit as the time to peak 13C detection did not differ between groups (4.9 ± 1.2 hours vs 4.7 ± 0.8 hours, P = .7). Rates of PA oxidation were not correlated with obesity, hepatic or adipose insulin resistance, alanine aminotransferase, liver fat content and NAFLD histology. Conclusion Fatty acid oxidation of orally delivered FA is decreased in NAFLD compared to healthy controls, likely reflecting decreased β‐oxidation. The use of a breath test offers non‐invasive dynamic assessment of FAO.

Common Transcriptional Program of Liver Fibrosis in Mouse Genetic Models and Humans

“…This common program is very similar to human NAFLD and NASH [18]. Downregulation of fatty acid metabolism and positive enrichment of platelets and hemostasis-related pathways is a hallmark of our data as well as transcriptomes of human NASH [19][20][21][22][23]. The negative enrichment of liver metabolic pathways indicates a molecular link between disrupted energy homeostasis and cell cycle control, which could be crucial for the development of NASH-related HCC [24].…”

“…This common program is very similar to human NAFLD and NASH [ 18 ]. Downregulation of fatty acid metabolism and positive enrichment of platelets and hemostasis-related pathways is a hallmark of our data as well as transcriptomes of human NASH [ 19 , 20 , 21 , 22 , 23 ].…”

Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

“…Diet has a relevant role in the development and progression of NAFLD, since a high energy intake and consumption of specific nutrients have a direct impact on the abnormal accumulation of TG in the liver, a hallmark of NAFLD [4]. High intake of nutrients that include saturated fatty acids (FA) such as palmitic acid (C16:0) [17][18][19] and trans FA of industrial origin [20] decrease FA oxidation (FAO), stimulate the synthesis and secretion of TGs, and trigger lipotoxic effects in the liver [4,17,18]. Moreover, high intake of n-6 PUFA, especially linoleic acid (C18:2n-6), and low consumption of n-3 LCPUFA (EPA and DHA) also appear to favor the development of hepatic steatosis [21].…”

Common transcriptional programme of liver fibrosis in mouse genetic models and humans

“…This common programme is very similar to human NAFLD and NASH (Teufel et al 2016). Downregulation of fatty acid metabolism and positive enrichment of platelets and haemostasis-related pathways is a hallmark of our data as well as transcriptomes of human NASH (Arendt et al 2015; Mardinoglu et al 2014; Moylan et al 2014; Ramadori et al 2019; Naguib et al 2020).…”