Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Objective: Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans.

Design: Cross-sectional study in men and women across a range of adiposity.

Methods: Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy.

Greater oxidation of dietary linoleate compared to palmitate in humans following an acute high-carbohydrate diet.

Background: We have previously demonstrated that dietary saturated fatty acids (SFA), when compared to polyunsaturated fatty acids (PUFA), are preferentially partitioned into oxidation pathways. However, it remains unclear if this preferential handling is maintained when hepatocellular metabolism is shifted toward fatty acid (FA) esterification and away from oxidation, such as when hepatic de novo lipogenesis (DNL) is upregulated.

Aim: To investigate whether an acute upregulation of hepatic DNL influences dietary FA partitioning into oxidation pathways.

Associations between types and sources of dietary carbohydrates and liver fat: a UK Biobank study.

Background And Aims: Excess energy intake can lead to metabolic dysfunction-associated steatotic liver disease (MASLD), but the relationship between dietary carbohydrate intake and liver fat content remains unclear. This study aimed to examine the associations between types and sources of dietary carbohydrates and liver fat content.

Methods: UK Biobank participants with no pre-existing diabetes, liver disease or cardiovascular disease reported dietary intake of types and sources of carbohydrates (total carbohydrates, free sugars, non-free sugars, starch from whole grains, starch from refined grains, and fibre) on at least two 24-h dietary assessments.

The effect of acute and chronic exercise on hepatic lipid composition.

Exercise is recommended for those with, or at risk of nonalcoholic fatty liver disease (NAFLD), owing to beneficial effects on hepatic steatosis and cardiometabolic risk. Whilst exercise training reduces total intrahepatic lipid in people with NAFLD, accumulating evidence indicates that exercise may also modulate hepatic lipid composition. This metabolic influence is important as the profile of saturated (SFA), monounsaturated (MUFA), and polyunsaturated fatty acids (PUFA) dramatically affect the metabolic consequences of hepatic lipid accumulation; with SFA being especially lipotoxic.

The influence of nutritional state on the fatty acid composition of circulating lipid fractions: implications for their use as biomarkers of dietary fat intake.

Background: The fatty acid (FA) composition of blood can be used as an objective biomarker of dietary FA intake. It remains unclear how the nutritional state influences the FA composition of plasma lipid fractions, and thus their usefulness as biomarkers in a non-fasted state.

Objectives: To investigate the associations between palmitate, oleate and linoleate in plasma lipid fractions and self-reported dietary FA intake, and assess the influence of meal consumption on the relative abundance of these FA in plasma lipid fractions (i.

Lifestyle interventions affecting hepatic fatty acid metabolism.

Purpose Of Review: Prevalence of metabolic-associated fatty liver disease (MAFLD) is increasing, and as pharmacological treatment does not exist, lifestyle interventions (i.e. diet and exercise) represent the cornerstone management and treatment strategy.

Oxidation of dietary linoleate occurs to a greater extent than dietary palmitate in vivo in humans.

Background: It has been suggested that dietary polyunsaturated fatty acids (PUFA) are partitioned into oxidation pathways to a greater extent than dietary saturated fatty acids (SFA). Whilst this has been demonstrated in animal models, evidence in humans is lacking. The potential divergence in the metabolic fate of these dietary fatty acids (FA) may explain some of the reported differences in ectopic fat deposition with SFA and PUFA enriched diets.

Using total plasma triacylglycerol to assess hepatic lipogenesis as an alternative to VLDL triacylglycerol.

Hepatic lipogenesis (DNL) is ideally measured in very low-density lipoprotein (VLDL)-triacylglycerol (TAG). In the fasting state, the majority of plasma TAG typically represents VLDL-TAG; however, the merits of measuring DNL in total plasma TAG have not been assessed. This study aimed to assess the performance of DNL measured in VLDL-TAG (DNL) compared to that measured in total plasma TAG (DNL).

Intrahepatic Fat and Postprandial Glycemia Increase After Consumption of a Diet Enriched in Saturated Fat Compared With Free Sugars.

Objective: Debate continues regarding the influence of dietary fats and sugars on the risk of developing metabolic diseases, including insulin resistance and nonalcoholic fatty liver disease (NAFLD). We investigated the effect of two eucaloric diets, one enriched with saturated fat (SFA) and the other enriched with free sugars (SUGAR), on intrahepatic triacylglycerol (IHTAG) content, hepatic de novo lipogenesis (DNL), and whole-body postprandial metabolism in overweight males.

Research Design And Methods: Sixteen overweight males were randomized to consume the SFA or SUGAR diet for 4 weeks before consuming the alternate diet after a 7-week washout period.

Managing NAFLD in Type 2 Diabetes: The Effect of Lifestyle Interventions, a Narrative Review.

The prevalence of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) is increasing. As a strong association between these two diseases exist, it is unsurprising that the number of patients with coexisting NAFLD and T2D is also increasing. These patients display a deleterious metabolic profile (e.

Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium.

Neutrophils are implicated in the pathogenesis of atherosclerosis but are seldom detected in atherosclerotic plaques. We investigated whether neutrophil-derived microvesicles may influence arterial pathophysiology. Here we report that levels of circulating neutrophil microvesicles are enhanced by exposure to a high fat diet, a known risk factor for atherosclerosis.

Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men.

Background: 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.

Objective: The aim was to investigate the influence of hyperenergetic, high-fat feeding on circulating hepatokine concentrations, including the time course of responses.

High-Fat Overfeeding Impairs Peripheral Glucose Metabolism and Muscle Microvascular eNOS Ser1177 Phosphorylation.

Context: The mechanisms responsible for dietary fat-induced insulin resistance of skeletal muscle and its microvasculature are only partially understood.

Objective: To determine the impact of high-fat overfeeding on postprandial glucose fluxes, muscle insulin signaling, and muscle microvascular endothelial nitric oxide synthase (eNOS) content and activation.

Design: Fifteen non-obese volunteers consumed a high-fat (64%) high-energy (+47%) diet for 7 days.

The influence of dietary fatty acids on liver fat content and metabolism.

Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver.

Fasting hepatic de novo lipogenesis is not reliably assessed using circulating fatty acid markers.

Background: Observational studies often infer hepatic de novo lipogenesis (DNL) by measuring circulating fatty acid (FA) markers; however, it remains to be elucidated whether these markers accurately reflect hepatic DNL.

Objectives: We investigated associations between fasting hepatic DNL and proposed FA markers of DNL in subjects consuming their habitual diet.

Methods: Fasting hepatic DNL was assessed using 2H2O (deuterated water) in 149 nondiabetic men and women and measuring the synthesis of very low-density lipoprotein triglyceride (VLDL-TG) palmitate.

GDF15 Provides an Endocrine Signal of Nutritional Stress in Mice and Humans.

GDF15 is an established biomarker of cellular stress. The fact that it signals via a specific hindbrain receptor, GFRAL, and that mice lacking GDF15 manifest diet-induced obesity suggest that GDF15 may play a physiological role in energy balance. We performed experiments in humans, mice, and cells to determine if and how nutritional perturbations modify GDF15 expression.

Studying non-alcoholic fatty liver disease: the ins and outs of in vivo, ex vivo and in vitro human models.

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. Determining the pathogenesis and pathophysiology of human NAFLD will allow for evidence-based prevention strategies, and more targeted mechanistic investigations. Various in vivo, ex situ and in vitro models may be utilised to study NAFLD; but all come with their own specific caveats.

Resistance exercise stimulates mixed muscle protein synthesis in lean and obese young adults.

Obese individuals exhibit a diminished muscle protein synthesis response to nutrient stimulation when compared with their lean counterparts. However, the effect of obesity on exercise-stimulated muscle protein synthesis remains unknown. Nine lean (23.

Chylomicron-Derived Fatty Acid Spillover in Adipose Tissue: A Signature of Metabolic Health?

Context And Objectives: Spillover of fatty acids (FAs) into the plasma nonesterified fatty acid (NEFA) pool, because of an inability of adipose tissue (AT) to accommodate sufficient fat uptake, has been suggested to contribute to obesity-related insulin resistance. Using specific labeling techniques, we compared the proportion of spillover-derived NEFA across a range of adiposity.

Participants And Methods: Seventy-one healthy men and women were fed a mixed meal (40 g fat) containing [U13C]palmitate to assess the contribution of chylomicron-derived spillover FAs.

Influence of dietary macronutrients on liver fat accumulation and metabolism.

The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role.

A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin Sensitivity: The Metabolic Consequence of Binge Eating.

Consuming excessive amounts of energy as dietary fat for several days or weeks can impair glycemic control and reduce insulin sensitivity in healthy adults. However, individuals who demonstrate binge eating behavior overconsume for much shorter periods of time; the metabolic consequences of such behavior remain unknown. The aim of this study was to determine the effect of a single day of high-fat overfeeding on whole-body insulin sensitivity.

Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals.

Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding.