ABSTRACT Interleukin-6 (IL-6), produced by skeletal muscle and extramuscular tissues, regulates skeletal muscle function through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. However, the interaction between intrinsic (locally produced) IL-6 and extrinsic (circulating) IL-6 in skeletal muscle remains unclear. We investigated whether and how intrinsic expression of IL-6 in cultured primary human myoblasts influences their response to extrinsic stimulation with recombinant human IL-6 (rhIL-6). Using gene silencing, we found that suppression of intrinsic IL-6 enhanced rhIL-6-induced phosphorylation of STAT1 and STAT3. Silencing STAT3 also increased rhIL-6-induced STAT1 phosphorylation, but silencing STAT1 had no effect on STAT3 phosphorylation. Pretreatment of myoblasts with neutralising anti-IL-6 antibodies increased phosphorylation of STAT1 and STAT3 induced by 50 ng/mL rhIL-6, whereas pretreatment with 5 ng/mL rhIL-6 reduced this response. Despite increased JAK/STAT signalling, IL-6 silencing decreased glucose and oleic acid uptake and oxidation under both basal and rhIL-6-stimulated conditions. Collectively, our results imply that intrinsic IL-6 restrains activation of the JAK/STAT pathway by extrinsic IL-6, but acts synergistically with it to promote myoblast energy metabolism.

The fusion index (FI) is widely used to assess myoblast differentiation into myotubes, but manual quantification is tedious and biased. Existing automated methods face limitations in nucleus segmentation and classification and often misidentify myoblast nuclei located above or below myotubes, leading to FI overestimation. To address these issues, we developed MyoFuse, an AI-based workflow enabling fully automated and unbiased FI quantification. MyoFuse combines nucleus segmentation using Cellpose with a classification network trained with Svetlana on fluorescence images of mouse C2C12 and human primary myotubes. Performance was evaluated by comparing MyoFuse-derived FI values with expert annotations and by assessing classification accuracy at the single-nucleus level. MyoFuse achieved strong accuracy scores in mouse C2C12 and human primary myotubes (0.954 and 0.911 respectively), and showed strong correlations with expert-derived FI values (r = 0.991 and r = 0.937 respectively; p < 0.0001). Unlike current approaches that overestimate FI, MyoFuse reliably segments nuclei even within dense clusters and distinguishes myotube from myoblast nuclei based solely on cytoplasmic staining. By processing large images, it further reduces selection bias and accounts for heterogeneity in myotube density. MyoFuse thus provides a robust, high-throughput, and accurate method for FI quantification in skeletal muscle cell culture.

Supplementation with krill oil has shown effects on whole-body lipid and glucose metabolism, as well as on skeletal muscle strength and function. We previously showed that krill oil intervention in vivo promoted fatty acid metabolism and protein synthesis in cultured human myotubes in a two-dimensional (2D) model. The aim of this study was to explore the effects of krill oil supplementation in vivo in a 3D myosphere model, and to compare a the human skeletal muscle 3D cell model to a 2D model. Myospheres were formed from myoblasts obtained before and after 7 weeks of in vivo krill oil intervention. Glucose and oleic acid metabolism were assessed, and transcriptomic and proteomic analyses were performed. In vivo intervention with krill oil increased glucose metabolism in myospheres, while no effect was observed on fatty acid metabolism. Transcriptomic analyses of myospheres after krill oil intervention showed increased expression of genes involved in pathways like motor proteins and hypertrophy, as well as in calcium signaling, of which motor proteins and hypertrophy pathways have not been described in 2D myotube cultures. Proteomic analyses after krill oil intervention showed increased expression of proteins in glycolysis/gluconeogenesis and fatty acid degradation. Comparison of proteins expressed in the 3D myosphere model and the 2D myotube model at the basal level showed that in myospheres, mitochondrial gene expression and translation dominated, while in 2D cultures, mitochondrial organization and response to oxidative stress were more important. These findings suggest that in vivo krill oil intervention induces different metabolic effects when comparing 3D and 2D cultures. In contrast to the 2D model, data obtained with the 3D model showed gene expression changes that are more compatible with previously observed results in vivo concerning skeletal muscle motoric function. Hence, the 3D cell model might better reflect krill oil-induced modifications in skeletal muscle performance in vivo than the 2D model.

[This corrects the article DOI: 10.3389/fbioe.2023.1130693.].

The abbreviation PDK1 may refer to two different proteins: pyruvate dehydrogenase kinase 1 and 3-phosphoinositide-dependent protein kinase 1. This overlap introduces ambiguity, making it challenging to discern which protein is being referenced. Here, we highlight widespread confusion surrounding PDK1, including cases where articles have stated incorrect antibodies, referred to incorrect sequences for PCR, gene silencing, or plasmid construction, merged the properties of pyruvate dehydrogenase kinase 1 and 3-phosphoinositide-dependent protein kinase 1, or incorrectly cited the other protein. Notably, 19 % of articles with the term “PDK1” on PubMed, published between 2019 and the middle of 2025, contain at least one such mistake. This ambiguity extends beyond the scientific literature to websites of biotechnology providers and vendors, where antibodies or recombinant proteins are misattributed. To mitigate this issue, the use of unique protein abbreviations, clear antibody and sequence identification, and a more rigorous peer review process are needed.

Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) plays a crucial role in regulation of metabolic homeostasis. To understand the role of the catalytic α2 subunit of AMPK in skeletal muscle energy metabolism, myotube cultures were established from AMPKα2+/+ and AMPKα2-/- mice. Myotubes from AMPKα2-/- mice had lower basal oleic acid and glucose oxidation compared to myotubes from AMPKα2+/+ mice. However, the relative response to mitochondrial uncoupling was increased for oleic acid oxidation. Incorporation of acetate into lipids was also lower in myotubes from AMPKα2-/- mice. Proteomics analysis revealed that AMPKα2-/- myotubes had upregulated pathways related to mitochondrial function and fatty acid oxidation, and decreased pathways related to fatty acid biosynthesis. In conclusion, ablation of AMPKα2 catalytic subunit in skeletal muscle cells resulted in reduced basal oxidation of glucose and fatty acids, however upregulated pathways related to mitochondrial function and fatty acid oxidation and reduced lipid formation.

Branched-chain fatty acids (BCFAs) are predominantly saturated fatty acids with one or more methyl branches on the carbon chain, typically found in dairy products and measured in micromolar concentrations in human plasma. The biological function of BCFAs in humans remains ill-defined, but a relationship between circulating BCFAs and cardiometabolic health has been suggested. The objective of this study was to evaluate the impact of BCFAs on energy metabolism in human myotubes. The results revealed distinct effects of BCFAs. 12-Methyltetradecanoic acid (12-MTD) increased glucose uptake and glycogen synthesis, while 13-methyltetradecanoic acid (13-MTD), 14-methylhexadecanoic acid (14-MHD), and 15-methylhexadecanoic acid (15-MHD) increased oleic acid uptake and 13-MTD and 15-MHD oleic acid oxidation, indicating a more general stimulatory effect on fatty acid than glucose metabolism. Interestingly, the same BCFAs, 13-MTD, 14-MHD, and 15-MHD, appeared to reduce insulin-stimulated glycogen synthesis. Insulin-stimulated phosphorylation of IRS1 was not apparent after exposure to 12-MTD, 13-MTD, and 15-MHD, whereas insulin-stimulated phosphorylation of Akt was unchanged by BCFAs. Incorporation of [14C]leucine into lipids was affected, as 13-MTD increased the total lipid content, and 12-MTD altered the distribution of lipid classes. Metabolic flux analysis indicated that 14-MHD stimulated extracellular acidification. The effects of BCFAs might involve increased mRNA expression of pyruvate dehydrogenase kinase 4. In conclusion, the study demonstrates that different BCFAs have distinct effects on energy metabolism in myotubes, 12-MTD mainly affect glucose metabolism, while 13-MTD, 14-MHD, and 15-MHD modulated oleic acid metabolism. These data suggest that some BCFAs might have therapeutic applications by improving energy metabolism.

In this study we investigated the potential for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) to modify energy metabolism in human primary skeletal muscle cells and mouse C2C12 skeletal muscle cells. The results showed that treatment of human myotubes with EMPA for 96 h decreased oxidation of exogenously added glucose and acetoacetate measured as CO2 production, whereas CO2 production from exogenously added fatty acids and leucine was increased compared to control cells. Uptake of acetoacetate by the cells was decreased by EMPA. Moreover, there were no EMPA-induced changes in glucose, fatty acid or leucine uptake by human myotubes, neither was lactate concentration in cell culture medium changed after exposure to EMPA. Treatment with EMPA increased phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in human myotubes, while there was no effect of EMPA in human myotubes on gene expression of selected metabolic genes. Real time cell metabolic analysis in C2C12 cells showed that EMPA reduced basal respiration and glycolysis, while under conditions promoting use of endogenous fatty acids, maximal respiration and ATP production was increased by EMPA. In summary, treatment of skeletal muscle cells in vitro with EMPA caused changes in energy metabolism promoting enhanced fatty acid and leucine catabolism, decreased metabolism of glucose and acetoacetate, and reduced glycolysis. The observed changes in energy metabolism may be related to AMPK activation.

Introduction:Marine oils and fatty fish rich in long-chain n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA), have been reported to enhance fatty acid (FA) oxidation and reduce plasma triacylglycerol and cholesterol levels. In addition to n-3 PUFAs, herring oil contains long-chain monounsaturated fatty acids (MUFAs), including cetoleic acid (C22:1n-11). This study aimed to investigate the effect of consuming CETO3® oil-derived from herring and naturally rich in n-3 PUFAs and cetoleic acid-on plasma lipid levels, FA composition, mitochondrial oxidation, and inflammation in rats. Methods:Rats were fed low-fat diets supplemented with 5% CETO3® oil (experimental) or soy oil (control) for 10 weeks. Plasma lipid profile (triglycerides (TG), total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) and FA composition in both liver and plasma were analyzed. In vitro substrate oxidation was assessed using ¹⁴CO₂-trapping in human liver and human myotubes. Safety parameters, including blood hematology, glucose tolerance, and organ weights, were also measured. Results:CETO3® supplementation decreased plasma levels of total fat (-58%), TG (-55%), total cholesterol (-41%), and LDL cholesterol (-45%), while increasing the ratio of HDL to LDL cholesterol (46%). Supplementation also increased hepatic and plasma levels of long-chain n-3, n-9, and n-11 MUFAs, including C22:1n-11, and decreased n-6 FA accumulation. The reduction in saturated long-chain FAs in both the liver and plasma indicated increased hepatic peroxisomal and mitochondrial activity. Furthermore, increased oleic acid oxidation was observed in human myotubes in the presence of C20:1n-11 and C20:1n-9. Discussion:These findings suggest that intake of CETO3® oil lowers plasma lipids, potentially through enhanced peroxisomal and mitochondrial FA oxidation. The shift in FA composition, with reduced n-6 FAs and increased n-3 and n-11 MUFAs, indicates an anti-inflammatory effect. CETO3® oil also appears safe, as hematological parameters, glucose tolerance, and organ weights remained unaffected.

IntroductionKrill oil is a dietary supplement derived from Antarctic krill; a small crustacean found in the ocean. Krill oil is a rich source of omega-3 fatty acids, specifically eicosapentaenoic acid and docosahexaenoic acid, as well as the antioxidant astaxanthin. The aim of this study was to investigate the effects of krill oil supplementation, compared to placebo oil (high oleic sunflower oil added astaxanthin), in vivo on energy metabolism and substrate turnover in human skeletal muscle cells.MethodsSkeletal muscle cells (myotubes) were obtained before and after a 7-week krill oil or placebo oil intervention, and glucose and oleic acid metabolism and leucine accumulation, as well as effects of different stimuli in vitro, were studied in the myotubes. The functional data were combined with proteomic and transcriptomic analyses.ResultsIn vivo intervention with krill oil increased oleic acid oxidation and leucine accumulation in skeletal muscle cells, however no effects were observed on glucose metabolism. The krill oil-intervention-induced increase in oleic acid oxidation correlated negatively with changes in serum low-density lipoprotein (LDL) concentration. In addition, myotubes were also exposed to krill oil in vitro. The in vitro study revealed that 24 h of krill oil treatment increased both glucose and oleic acid metabolism in myotubes, enhancing energy substrate utilization. Transcriptomic analysis comparing myotubes obtained before and after krill oil supplementation identified differentially expressed genes associated with e.g., glycolysis/gluconeogenesis, metabolic pathways and calcium signaling pathway, while proteomic analysis demonstrated upregulation of e.g., LDL-receptor in myotubes obtained after the krill oil intervention.ConclusionThese findings suggest that krill oil intervention promotes increased fuel metabolism and protein synthesis in human skeletal muscle cells, with potential implications for metabolic health.

In addition to its antiatherogenic role, HDL reportedly modulates energy metabolism at the whole-body level. HDL functionality is associated with its structure and composition, and functional activities can differ between HDL subclasses. Therefore, we studied if HDL2 and HDL3, the two major HDL subclasses, are able to modulate energy metabolism of skeletal muscle cells. Differentiated mouse and primary human skeletal muscle myotubes were used to investigate the influences of human HDL2 and HDL3 on glucose and fatty uptake and oxidation. HDL-induced changes in lipid distribution and mRNA expression of genes related to energy substrate metabolism, mitochondrial function, and HDL receptors were studied with human myotubes. Additionally, we examined the effects of apoA-I and discoidal, reconstituted HDL particles on substrate metabolism. In mouse myotubes, HDL subclasses strongly enhanced glycolysis upon high and low glucose concentrations. HDL3 caused a minor increase in ATP-linked respiration upon glucose conditioning but HDL2 improved complex I–mediated mitochondrial respiration upon fatty acid treatment. In human myotubes, glucose metabolism was attenuated but fatty acid uptake and oxidation were markedly increased by both HDL subclasses, which also increased mRNA expression of genes related to fatty acid metabolism and HDL receptors. Finally, both HDL subclasses induced incorporation of oleic acid into different lipid classes. These results, demonstrating that HDL subclasses enhance fatty acid oxidation in human myotubes but improve anaerobic metabolism in mouse myotubes, support the role of HDL as a circulating modulator of energy metabolism. Exact mechanisms and components of HDL causing the change, require further investigation.

Skeletal muscle has an important role in whole body energy metabolism and various proteases are involved in skeletal muscle functions. We have previously identified the cysteine protease legumain in cultured human skeletal muscle cells. However, the potential role of legumain in regulation of energy metabolism remains unexplored. This study aimed to investigate cellular uptake, processing, and activation of prolegumain in human myotubes. Additionally, we sought to determine the effects of prolegumain on energy substrate metabolism in these cells. During differentiation of human myoblast to myotubes, legumain mRNA expression and activity were upregulated. Interestingly, legumain activity in myotubes was inversely correlated with the body mass index (BMI) of the obese cell donors. Myotubes exposed to conditioned medium enriched in prolegumain during the last two days of differentiation demonstrated the capacity to internalize and process prolegumain into its active form. Pre-treatment with prolegumain induced a metabolic shift towards increased fatty acid uptake in myotubes, as evidenced by elevated oleic acid uptake whereas glucose uptake and oxidation were reduced. The metabolic changes were not reversed by a legumain inhibitor, indicating a different mechanism for this effect. The metabolic alterations were accompanied by increased mRNA expression of the fatty acid transporter CD36, whereas the glucose transporter GLUT1 mRNA level remained unchanged. These findings suggest that legumain may play a regulatory role in skeletal muscle energy metabolism, highlighting its potential as a novel therapeutic target of metabolic disorders.

BACKGROUND:Skeletal muscle adapts in reaction to contractile activity to efficiently utilize energy substrates, primarily glucose and free fatty acids (FA). Inactivity leads to atrophy and a change in energy utilization in individuals with spinal cord injury (SCI). The present study aimed to characterize possible inactivity-related differences in the energy metabolism between skeletal muscle cells cultured from satellite cells isolated 1- and 12-months post-SCI. METHODS:To characterize inactivity-related disturbances in spinal cord injury, we studied skeletal muscle cells isolated from SCI subjects. Cell cultures were established from biopsy samples from musculus vastus lateralis from subjects with SCI 1 and 12 months after the injury. The myoblasts were proliferated and differentiated into myotubes before fatty acid and glucose metabolism were assessed and gene and protein expressions were measured. RESULTS:The results showed that glucose uptake was increased, while oleic acid oxidation was reduced at 12 months compared to 1 month. mRNA expressions of PPARGC1α, the master regulator of mitochondrial biogenesis, and MYH2, a determinant of muscle fiber type, were significantly reduced at 12 months. Proteomic analysis showed reduced expression of several mitochondrial proteins. CONCLUSION:In conclusion, skeletal muscle cells isolated from immobilized subjects 12 months compared to 1 month after SCI showed reduced fatty acid metabolism and reduced expression of mitochondrial proteins, indicating an increased loss of oxidative capacity with time after injury.

Introduction: Skeletal muscle is a major contributor to whole-body energy homeostasis and the utilization of fatty acids and glucose. At present, 2D cell models have been the most used cellular models to study skeletal muscle energy metabolism. However, the transferability of the results to in vivo might be limited. This project aimed to develop and characterize a skeletal muscle 3D cell model (myospheres) as an easy and low-cost tool to study molecular mechanisms of energy metabolism. Methods and results: We demonstrated that human primary myoblasts form myospheres without external matrix support and carry structural and molecular characteristics of mature skeletal muscle after 10 days of differentiation. We found significant metabolic differences between the 2D myotubes model and myospheres. In particular, myospheres showed increased lipid oxidative metabolism than the 2D myotubes model, which oxidized relatively more glucose and accumulated more oleic acid. Discussion and conclusion: These analyses demonstrate model differences that can have an impact and should be taken into consideration for studying energy metabolism and metabolic disorders in skeletal muscle.

Objective: Non-shivering thermogenesis (NST) mediated by uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) can be activated via the adrenergic system in response to cold or diet, contributing to both thermal and energy homeostasis. Other mechanisms, including metabolism of skeletal muscle, may also be involved in NST. However, relative contribution of these energy dissipating pathways and their adaptability remain a matter of long-standing controversy.Methods: We used warm-acclimated (30 degrees C) mice to characterize the effect of an up to 7-day cold acclimation (6 degrees C; CA) on thermoregulatory thermogenesis, comparing inbred mice with a genetic background conferring resistance (A/J) or susceptibility (C57BL/6 J) to obesity.Results: Both warm-acclimated C57BL/6 J and A/J mice exhibited similar cold endurance, assessed as a capability to maintain core body temperature during acute exposure to cold, which improved in response to CA, resulting in comparable cold endurance and similar induction of UCP1 protein in BAT of mice of both genotypes. Despite this, adrenergic NST in BAT was induced only in C57BL/6 J, not in A/J mice subjected to CA. Cold tolerance phenotype of A/J mice subjected to CA was not based on increased shivering, improved insulation, or changes in physical activity. On the contrary, lipidomic, proteomic and gene expression analyses along with palmitoyl carnitine oxidation and cytochrome c oxidase activity revealed induction of lipid oxidation exclusively in skeletal muscle of A/J mice subjected to CA. These changes appear to be related to skeletal muscle NST, mediated by sarcolipin-induced uncoupling of sarco(endo)plasmic reticulum calcium ATPase pump activity and accentuated by changes in mitochondrial respiratory chain supercomplexes assembly. Conclusions: Our results suggest that NST in skeletal muscle could be adaptively augmented in the face of insufficient adrenergic NST in BAT, depending on the genetic background of the mice. It may provide both protection from cold and resistance to obesity, more effectively than BAT.(c) 2023 The Author(s). Published by Elsevier GmbH. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

The interplay between skeletal muscle and bone is primarily mechanical; however, biochemical crosstalk by secreted mediators has recently gained increased attention. The aim of this study was to investigate metabolic effects of conditioned medium from osteoblasts (OB-CM) on myotubes and vice versa. Human skeletal muscle cells incubated with OB-CM showed increased glucose uptake and oxidation, and mRNA expression of the glucose transporter (GLUT) 1, while fatty acid uptake and oxidation, and mRNA expression of the fatty acid transporter CD36 were decreased. This was supported by proteomic analysis, where expression of proteins involved in glucose uptake, glycolytic pathways, and the TCA cycle were enhanced, and expression of several proteins involved in fatty acid metabolism were reduced. Similar effects on energy metabolism were observed in human bone marrow stromal cells differentiated to osteoblastic cells incubated with conditioned medium from myotubes (SKM-CM), with increased glucose uptake and reduced oleic acid uptake. Proteomic analyses of the two conditioned media revealed many common proteins. Thus, our data may indicate a shift in fuel preference from fatty acid to glucose metabolism in both cell types, induced by conditioned media from the opposite cell type, possibly indicating a more general pattern in communication between these tissues.

Adipose tissue is one of the main regulative sites for energy metabolism. Excess lipid storage and expansion of white adipose tissue (WAT) is the primary contributor to obesity, a strong predisposing factor for development of insulin resistance. Sentrin-specific protease (SENP) 2 has been shown to play a role in metabolism in murine fat and skeletal muscle cells, and we have previously demonstrated its role in energy metabolism of human skeletal muscle cells. In the present work, we have investigated the impact of SENP2 on fatty acid and glucose metabolism in primary human fat cells by using cultured primary human adipocytes to knock down the SENP2 gene. Glucose uptake and oxidation, as well as accumulation and distribution of oleic acid into complex lipids were decreased, while oleic acid oxidation was increased in SENP2-knockdown cells compared to control adipocytes. Furthermore, lipogenesis was reduced by SENP2-knockdown in adipocytes. Although TAG accumulation relative to total uptake was unchanged, there was increased mRNA expression of metabolically relevant genes such as UCP1 and PPARGC1A and mRNA and proteomic data revealed increased levels of mRNA and proteins related to mitochondrial function by SENP2-knockdown. In conclusion, SENP2 is an important regulator of energy metabolism in primary human adipocytes and its knockdown reduce glucose metabolism and lipid accumulation, while increasing lipid oxidation in human adipocytes.

BackgroundParenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.MethodsTwo in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro.ResultsIn the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake.ConclusionsSEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.