Summary: This systematic review and meta‐analysis determined the impact of structured exercise training, and the influence of associated weight loss, on intrahepatic triglyceride (IHTG) in individuals with non‐alcoholic fatty liver disease (NAFLD). It also examined its effect on hepatic insulin sensitivity in individuals with or at increased risk of NAFLD. Analyses were restricted to studies using magnetic resonance spectroscopy or liver biopsy for the measurement of IHTG and isotope‐labelled glucose tracer for assessment of hepatic insulin sensitivity. Pooling data from 17 studies (373 exercising participants), exercise training for one to 24 weeks (mode: 12 weeks) elicits an absolute reduction in IHTG of 3.31% (95% CI: −4.41 to −2.22%). Exercise reduces IHTG independent of significant weight change (−2.16 [−2.87 to −1.44]%), but benefits are substantially greater when weight loss occurs (−4.87 [−6.64 to −3.11]%). Furthermore, meta‐regression identified a positive association between percentage weight loss and absolute reduction in IHTG (β = 0.99 [0.62 to 1.36], P < 0.001). Pooling of six studies (94 participants) suggests that exercise training also improves basal hepatic insulin sensitivity (mean change in hepatic insulin sensitivity index: 0.13 [0.05 to 0.21] mg m⁻² min⁻¹ per μU mL⁻¹), but available evidence is limited, and the impact of exercise on insulin‐stimulated hepatic insulin sensitivity remains unclear.

Obesity is a primary antecedent to non-alcoholic fatty liver disease whose cardinal feature is excessive hepatic lipid accumulation. Although total hepatic lipid content closely associates with hepatic and systemic metabolic dysfunction, accumulating evidence suggests that the composition of hepatic lipids may be more discriminatory. This review summarises cross-sectional human studies using liver biopsy/lipidomics and proton magnetic resonance spectroscopy to characterise hepatic lipid composition in people with obesity and related metabolic disease. A comprehensive literature search identified 26 relevant studies published up to 31^st March 2021 which were included in the review. The available evidence provides a consistent picture showing that people with hepatic steatosis possess elevated saturated and/or monounsaturated hepatic lipids and a reduced proportion of polyunsaturated hepatic lipids. This altered hepatic lipid profile associates more directly with metabolic derangements, such as insulin resistance, and may be exacerbated in non-alcoholic steatohepatitis. Further evidence from lipidomic studies suggests that these deleterious changes may be related to defects in lipid desaturation and elongation, and an augmentation of the de novo lipogenic pathway. These observations are consistent with mechanistic studies implicating saturated fatty acids and associated bioactive lipid intermediates (ceramides, lysophosphatidylcholines and diacylglycerol) in the development of hepatic lipotoxicity and wider metabolic dysfunction, whilst monounsaturated fatty acids and polyunsaturated fatty acids may exhibit a protective role. Future studies are needed to prospectively determine the relevance of hepatic lipid composition for hepatic and non-hepatic morbidity and mortality; and to further evaluate the impact of therapeutic interventions such as pharmacotherapy and lifestyle interventions.

Background and aims: Smokers typically have a lower body mass index (BMI) than non‐smokers, while smoking cessation is associated with weight gain. In pre‐clinical research, nicotine in tobacco smoking suppresses appetite and influences subsequent eating behaviour; however, this relationship is unclear in humans. This study measured the associations of smoking with different eating and dietary behaviours.Design: A cross‐sectional analysis of data from health assessments conducted between 2004 and 2022.Setting: An independent healthcare‐based charity within the United Kingdom.Participants: A total of 80 296 men and women (mean ± standard deviation [SD]: age, 43.0 ± 10.4 years; BMI, 25.7 ± 4.2 kg/m²; 62.5% male) stratified into two groups based on their status as a smoker (n = 6042; 7.5%) or non‐smoker (n = 74 254; 92.5%).Measurements: Smoking status (self‐report) was the main exposure, while the primary outcomes were selected eating and dietary behaviours. Age, sex and socioeconomic status (index of multiple deprivation [IMD]) were included as covariates and interaction terms, while moderate‐to‐vigorous exercise and sleep quality were included as covariates only.Findings: Smokers had lower odds of snacking between meals and eating food as a reward or out of boredom versus non‐smokers (all odds ratio [OR] ≤ 0.82; P < 0.001). Furthermore, smokers had higher odds of skipping meals, going more than 3 h without food, adding salt and sugar to their food, overeating and finding it hard to leave something on their plate versus non‐smokers (all OR ≥ 1.06; P ≤ 0.030). Additionally, compared with non‐smokers, smoking was associated with eating fried food more times per week (rate ratio [RR] = 1.08; P < 0.001), eating fewer meals per day, eating sweet foods between meals and eating dessert on fewer days per week (all RR ≤ 0.93; P < 0.001). Several of these relationships were modified by age, sex and IMD.Conclusions: Smoking appears to be associated with eating and dietary behaviours consistent with inhibited food intake, low diet quality and altered food preference. Several of these relationships are moderated by age, sex and socioeconomic status.

Hepatokines such as fibroblast growth factor 21 (FGF21), leukocyte cell-derived chemotaxin 2 (LECT2), fetuin-A, fetuin-B, and selenoprotein P (SeP) are liver-derived proteins that are modulated by chronic energy status and metabolic disease. Emerging data from rodent and cell models indicate that hepatokines may be sensitive to acute nutritional manipulation; however, data in humans are lacking. The aim was to investigate the influence of hyperenergetic, high-fat feeding on circulating hepatokine concentrations, including the time course of responses. In a randomized, crossover design, 12 healthy men [mean ± SD: age, 24 ± 4 y; BMI (kg/m2), 24.1 ± 1.5] consumed a 7-d hyperenergetic, high-fat diet [HE-HFD; +50% energy, 65% total energy as fat (32% saturated, 26% monounsaturated, 8% polyunsaturated)] and control diet (36% total energy as fat), separated by 3 wk. Whole-body insulin sensitivity was assessed before and after each diet using oral-glucose-tolerance tests. Fasting plasma concentrations of FGF21 (primary outcome), LECT2, fetuin-A, fetuin-B, SeP, and related metabolites were measured after 1, 3, and 7 d of each diet. Hepatokine responses were analyzed using 2-factor repeated-measures ANOVA and subsequent pairwise comparisons. Compared with the control, the HE-HFD increased circulating FGF21 at 1 d (105%) and 3 d (121%; P ≤ 0.040), LECT2 at 3 d (17%) and 7 d (32%; P ≤ 0.004), and fetuin-A at 7 d (7%; P = 0.028). Plasma fetuin-B and SeP did not respond to the HE-HFD. Whole-body insulin sensitivity was reduced after the HE-HFD by 31% (P = 0.021). Acute high-fat overfeeding augments circulating concentrations of FGF21, LECT2, and fetuin-A in healthy men. Notably, the time course of response varies between proteins and is transient for FGF21. These findings provide further insight into the nutritional regulation of hepatokines in humans and their interaction with metabolic homeostasis. This study was registered at clinicaltrials.gov as NCT03369145.

Physical activity (PA) is recommended in the management of non-alcoholic fatty liver disease (NAFLD) given its beneficial effects on liver fat and cardiometabolic risk. Using data from the UK Biobank population-cohort, this study examined associations between habitual PA and hepatic fibro-inflammation. A total of 840 men and women aged 55-70 years were included in this cross-sectional study. Hepatic fibro-inflammation (iron-corrected T1 [cT1]) and liver fat were measured using MRI, whilst body fat was measured using dual-energy X-ray absorptiometry. PA was measured using accelerometry. Generalised linear models examined associations between PA (light [LPA], moderate [MPA], vigorous [VPA], moderate-to-vigorous [MVPA] and mean acceleration) and hepatic cT1. Models were fitted for the whole sample and separately for upper and lower median groups for body and liver fat. Models were adjusted for sociodemographic and lifestyle variables. In the full sample, LPA (-0.08 ms [-0.12 to -0.03]), MPA, (-0.13 ms [-0.21 to -0.05]), VPA (-1.16 ms [-1.81 to -0.51]), MVPA (-0.14 ms [-0.21 to -0.06]) and mean acceleration (-0.67 ms [-1.05 to-0.28]) were inversely associated with hepatic cT1. With the sample split by median liver or body fat, only VPA was inversely associated with hepatic cT1 in the upper median groups for body (-2.68 ms [-4.24 to -1.13]) and liver fat (-2.33 [-3.73 to -0.93]). PA was unrelated to hepatic cT1 in the lower median groups. Within a population-based cohort, device-measured PA is inversely associated with hepatic fibro-inflammation. This relationship is strongest with VPA and is greater in people with higher levels of body and liver fat. This study has shown that people who regularly perform greater amounts of physical activity have a reduced level of inflammation and fibrosis in their liver. This beneficial relationship is particularly strong when more intense physical activity is undertaken (i.e., vigorous-intensity), and is most visible in individuals with higher levels of liver fat and body fat.

The effect of football‐specific fatigue on explosive neuromuscular performance and dynamic balance has received little attention in the literature despite the potential consequences for injury risk. This study aimed to investigate the effect of fatigue induced by simulated football match play on maximal and explosive knee flexor (KF) and knee extensor (KE) torque, and thus the maximal and explosive KF/KE ratio, as well as the effect of fatigue induced by simulated football match play on whole‐body response to disturbances in balance. Fifteen male team sports players (mean ± SD: age 24.2 ± 4.2 years; stature 1.79 ± 0.09 m; body mass, 77.3 ± 10.7 kg) underwent ~90 minutes of the modified Loughborough Intermittent Shuttle Test (LIST; fatiguing exercise condition) or seated rest (control condition) on separate days. Maximal and explosive isometric KF and KE voluntary torque (MVT/EVT) were assessed pre‐ and post‐condition. Maximal and explosive KF/KE ratios were calculated. Center of mass (COM) response (displacement) to unexpected anterior and posterior platform perturbations were also assessed pre‐ and post‐condition. Football simulated fatigue resulted in reduced KF (15%) and KE (12%) MVT (P ≤ 0.002) but was not found to reduce EVT of either muscle group, or explosive KF/KE ratio. Football simulated fatigue resulted in impaired balance response (11% increase in COM displacement) to unexpected perturbation in the posterior (P = 0.002) but not the anterior direction. Impaired response to dynamic disturbances in balance, rather than explosive torque or changes in muscle balance (H/Q ratios), may be a contributory factor toward increased injury risk in the latter portion of football games, and likely highlights the influence of fatigue on sensory/proprioceptive processes.