The contribution of afferent signals from the liver to metabolic regulation during exercise

The crucial role of the liver as the only organ to produce glucose used by skeletal muscle during exercise is well known. Since hepatic glucose production is central to blood glucose homeostasis during exercise, it has been postulated that the liver may inform the central nervous system and other organs of its diminishing capacity to produce glucose from glycogen, before blood glucose falls. The sensory role of the liver during exercise would be similar to its role in the control of food intake. As a consequence, the experimental approaches used to test the hypothesis that afferent signals from the liver contribute to metabolic regulation during exercise are inspired by those used to test the same hypothesis in the regulation of food intake. In the present review, two questions are addressed. The existing evidence for the liver's sensory influence on metabolic adjustments to exercise is first reviewed; the nature of the initiating stimuli for the afferent contribution of the liver to physical exercise is discussed thereafter. The hypothetical construct upon which rests the contribution of the liver's afferent signals to metabolic regulation during exercise is that a decrease in liver glycogen or a related metabolic intermediate is sensed by the liver, and the signal is transduced to the central nervous system, most likely through the afferent activity of the hepatic vagus nerve, where it contributes to the orchestration of the metabolic and hormonal responses to exercise. Support in favour of this construct comes mainly from the demonstration that sectioning of the hepatic vagus nerve attenuates the normal hormonal response to exercise. It seems that the liver-glucagon axis is particularly responsive to this reflex activation. In other respects, the hepatic mechanism responsible for linking the metabolic activity in the liver to an afferent signal capable of regulating the metabolic response to exercise remains speculative. Substrates or derivatives of substrate oxidation, energy-related compounds (ATP and Pi), or changes in cell volume may all be related to changes in transmembrane potential in the liver cell, which according to the "potentiostatic" theory would determine the afferent vagal activity.     

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.     

Effect of liver glycogen content on glucose production in running rats

The influence of supranormal compared with normal hepatic glycogen levels on hepatic glucose production (Ra) during exercise was investigated in chronically catheterized rats. Supranormal hepatic glycogen levels were obtained by a 24-h fast-24-h refeeding regimen. During treadmill running for 35 min at a speed of 21 m/min, Ra and plasma glucose increased more (P less than 0.05) and liver glucogen breakdown was larger in fasted-refed compared with control rats, although the stimuli for Ra were higher in control rats, the plasma concentrations of insulin and glucose being lower (P less than 0.05) in control compared with fasted-refed rats. Also, plasma concentrations of glucagon and both catecholamines tended to be higher and muscle glycogenolysis lower in control compared with fasted-refed rats. Lipid metabolism was similar in the two groups. The results indicate that hepatic glycogenolysis during exercise is directly related to hepatic glycogen content. The smaller endocrine glycogenolytic signal in face of higher plasma glucose concentrations in fasted-refed compared with control rats is indicative of metabolic feedback control of glucose mobilization during exercise. However, the higher exercise-induced increase in Ra, plasma glucose, and liver glycogen breakdown in fasted-refed compared with control rats indicates that metabolic feedback mechanisms are not able to accurately match Ra to the metabolic needs of working muscles.     

Exercise and postprandial lipid metabolism: an update on potential mechanisms and interactions with high-carbohydrate diets (review)

Endurance trained people exhibit low levels of postprandial lipemia. However, this favorable situation is rapidly reversed with de-training and it is likely that the triglyceride (TG) lowering effects of exercise are mainly the result of acute metabolic responses to recent exercise rather than long-term training adaptations. A large body of evidence suggests that postprandial lipemia can be attenuated following an individual exercise session, with the energy expended during exercise being an important determinant of the extent of TG lowering. Increased lipoprotein lipase-mediated TG clearance and reduced hepatic TG secretion are both likely to contribute to the exercise-induced TG reductions. These changes may occur in response to post-exercise substrate deficits in skeletal muscle and/or the liver. In addition, regular exercise can oppose the hypertriglyceridaemia sometimes seen with low-fat, high-carbohydrate diets. Levels of physical activity should therefore be taken into account when considering nutritional strategies for reducing the risk of cardiovascular disease.     

Exercise ameliorates insulin resistance and improves ASK1-mediated insulin signalling in obese rats

Increasing evidence reveals that physical exercise is an efficient therapeutical approach in the treatment of insulin resistance (IR) and related metabolic diseases. However, the potential beneficial effects of exercise on insulin resistance and its underlying mechanisms remain unclear. Recent findings elucidated the negative role of ASK1 in repressing the glucose uptake through JNK1-IRS1-Akt signalling in liver. Thus, a detailed investigation of the effect of ASK1-mediated insulin signalling on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was implemented in this study. Using a high-fat diet-induced IR rat model of chronic or acute swimming exercise training, we here showed that body weight and visceral fat mass were significantly reduced after chronic exercise. Moreover, chronic exercise reduced serum FFAs levels and hepatic triglyceride content. Both chronic and acute exercise promoted glucose tolerance and insulin sensitivity. Meanwhile, both chronic and acute exercise decreased ASK1 phosphorylation and improved JNK1-IRS1-Akt signalling. Furthermore, exercise training decreased CFLAR, CREG and TRAF1 protein levels in liver of obese rats, which are positive regulator of ASK1 activity. These results suggested that swimming exercise demonstrated to be an effective ameliorator of IR through the regulation of ASK1-mediated insulin signalling and therefore, could present a prospective therapeutic mean towards the treatment of IR and several metabolic diseases based on IR, containing NAFLD and type Ⅱ diabetes.     

Lipoprotein kinetics in the metabolic syndrome: pathophysiological and therapeutic lessons from stable isotope studies

Dyslipoproteinaemia is a cardinal feature of the metabolic syndrome that accelerates atherosclerosis. It is usually characterised by high plasma concentrations of triglyceride-rich and apolipoprotein (apo) B-containing lipoproteins, with depressed concentrations of high-density lipoprotein (HDL). Dysregulation of lipoprotein metabolism in these subjects may be due to a combination of overproduction of very-low-density lipoprotein (VLDL) apoB-100, decreased catabolism of apoB-containing particles, and increased catabolism of HDL apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance that increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver, the increased hepatic secretion of VLDL-triglycerides and the remodelling of both low-density lipoprotein (LDL) and HDL particles in the circulation; perturbations in lipolytic enzymes and lipid transfer proteins contribute to the dyslipidaemia. Our in vivo understanding of the kinetic defects in lipoprotein metabolism in the metabolic syndrome has been chiefly achieved by ongoing developments in the use of stable isotope tracers and mathematical modelling. Knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications and increased physical exercise may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL apoA-I, as well as by increasing the clearance of LDL-apoB. Pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by several mechanisms of action including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary mechanisms of action of lifestyle and drug therapies support the use of combination regimens to treat dyslipidaemia in the metabolic syndrome.     

Free radical biology for medicine: learning from nonalcoholic fatty liver disease

Reactive oxygen species, when released under controlled conditions and limited amounts, contribute to cellular proliferation, senescence, and survival by acting as signaling intermediates. In past decades there has been an epidemic diffusion of nonalcoholic fatty liver disease (NAFLD) that represents the result of the impairment of lipid metabolism, redox imbalance, and insulin resistance in the liver. To date, most studies and reviews have been focused on the molecular mechanisms by which fatty liver progresses to steatohepatitis, but the processes leading toward the development of hepatic steatosis in NAFLD are not fully understood yet. Several nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) α/γ/δ, PPARγ coactivators 1α and 1β, sterol-regulatory element-binding proteins, AMP-activated protein kinase, liver-X-receptors, and farnesoid-X-receptor, play key roles in the regulation of lipid homeostasis during the pathogenesis of NAFLD. These nuclear receptors may act as redox sensors and may modulate various metabolic pathways in response to specific molecules that act as ligands. It is conceivable that a redox-dependent modulation of lipid metabolism, nuclear receptor-mediated, could cause the development of hepatic steatosis and insulin resistance. Thus, this network may represent a potential therapeutic target for the treatment and prevention of hepatic steatosis and its progression to steatohepatitis. This review summarizes the redox-dependent factors that contribute to metabolism alterations in fatty liver with a focus on the redox control of nuclear receptors in normal liver as well as in NAFLD.     

Effects of selective hepatic vagotomy on running endurance in rats

The liver, through the afferent ways of the vagus hepatic nerve, may influence metabolic adaptations during exercise. This study assesses the functional significance of this hepatic innervation by determining the effect of a selective hepatic vagotomy (HV) on running endurance time during submaximal activity in rats subjected to an overnight 50% food restriction. The time to exhaustion was similar for the groups of HV and sham-operated (SHM) rats [66 +/- 15 vs. 64 +/- 21 (SD) min]. The HV group was associated with higher resting levels (P less than 0.05) of hepatic glycogen and plasma glucose. No significant differences were observed between HV and SHM rats at rest and after exercise for muscle glycogen, free fatty acids, insulin, glucagon, and lactate concentrations. These data indicate that if hepatic glucoreceptors do exist and contribute to the metabolic regulation of exercise, their functional significance is secondary to more important regulatory mechanisms.     

A combined healthy strategy for successful weight loss,weight maintenance and improvement of hepatic lipid metabolism

Obesity is critically related with the development of metabolic and pathophysiological alterations among which non-alcoholic fatty liver disease (NAFLD) is of especial relevance. Although there are numerous strategies to successfully treat obesity, the prevention of weight regain still remains challenging for individuals who have undergone weight loss programs. In such context, diet and physical activity are considered essential for the regulation of body weight and lipid metabolism. In this study, rats were fed a high-fat diet (HFD) to induce obesity and alterations in hepatic lipid metabolism. Obese rats were then treated with single or combined strategies of caloric restriction, physical exercise, and/or pharmacological treatment with an appetite suppressant, to lose weight, reverse the obesity-related alterations in hepatic morphology and lipid metabolism and maintain the beneficial effects of the interventions used. HFD induced excess body weight, hepatic steatosis, altered fatty acid profile, dysregulated gene expression of lipogenic and lipolytic enzymes, as well as plasma markers of liver damage, and modifications in liver antioxidant enzyme activity. Such alterations were ameliorated by caloric restriction in combination with a mixed training protocol and/or food-intake inhibitor administration during a weight loss intervention period of 3 weeks, and the beneficial effects remained after 6 weeks of weight maintenance, with some interesting interactions observed. In conclusion, weight loss strategies assayed were efficient at correcting the obesogenic action of a HFD and related alterations in hepatic functionality through different molecular mechanisms. The beneficial effects were also evident along the post-intervention maintenance period to avoid body weight regain.     

A comparison of the metabolic effects of continuous hypothermic perfusion or oxygenated persufflation during hypothermic storage of rat liver

The metabolic consequences of supplying oxygen by two different modes were investigated. The effects of hypothermic liver preservation after cold hypoxic flush (Group I), oxygenated vascular persufflation (Group II), and continuous oxygenated perfusion (Group III) were compared. Adenine nucleotides were measured to assess energetics, and 1H nuclear magnetic resonance spectroscopy was employed to investigate other metabolic pathways. Energetics were maintained by both modes of oxygenation at 24 h. The mitochondrial redox state is indicated by the ratio of acetoacetate (Ace) and beta-hydroxybutyrate (betaHb). The detection of only betaHb or Ace in the hypoxic flush and perfused livers, respectively, suggested that the mitochondria of these livers were hyperreduced and hyperoxidized, respectively. In contrast, both components of the redox couple were detected in the persufflated livers, suggesting that persufflation may be a simple and effective method of maintaining hepatic energetics long-term while maintaining a more normal mitochondrial redox state.     

HSP70 as a biomarker of the thin threshold between benefit and injury due to physical exercise when exposed to air pollution

Physical exercise has acute and chronic effects on inflammatory balance, metabolic regulation, and redox status. Exercise-induced adaptations are mediated by enhanced 70-kDa heat shock protein (HSP70) levels and an improved heat shock response (HSR). Therefore, exercise could be useful against disease conditions [obesity, diabetes mellitus (DM), and exposure to atmospheric pollutants] marked by an impaired HSR. However, exercise performed by obese or diabetic subjects under pollution conditions might also be dangerous at certain intensities. Intensity correlates with an increase in HSP70 levels during physical exercise until a critical point at which the effort becomes harmful and impairs the HSR. Establishing a unique biomarker able to indicate the exercise intensity on metabolism and cellular fatigue is essential to ensure adequate and safe exercise recommendations for individuals with obesity or DM who require exercise to improve their metabolic status and live in polluted regions. In this review, we examined the available evidence supporting our hypothesis that HSP70 could serve as a biomarker for determining the optimal exercise intensity for subjects with obesity or diabetes when exposed to air pollution and establishing the fine threshold between anti-inflammatory and pro-inflammatory exercise effects.     

Interconnection of carbohydrate and lipid metabolism in various modes of muscle activity

The activity of hexokinase and lipase has been determined in skeletal muscles of different metabolic types and adipose tissue of untrained albino rats during two variations of predominant aerobic physical exercise: long-term swimming and long-term swimming including short-term loads (20 s) of maximal intensity (acceleration). Muscle and liver glycogen depletion, serum lactate, glucose and free fatty acids concentrations are also investigated. It is shown that long-term swimming (first variation) has promoted a decrease of both enzymatic activities in muscle fibres and an increase in lipolytic activity of the adipose tissue. During the physical exercise with the acceleration an increase in hexokinase activity occurs in response to 20 min swimming, with its maximal decrease in response to 40 min of exercise. Activity of lipase in slow-twitch oxidative fibres of soleus and in the adipose tissue increases from 20 min to the end of the exercise. Depletion of glycogen in the muscles and liver is determined in fast-twitch oxidative-glycolytic fibres and in the liver in two types of exercises, being more significant in muscles after exercise with accelerations. Concentrations of serum lactate, glucose and free fatty acids remain unchanged after both variations of swimming. So, it may be concluded that acute adaptation to the predominant aerobic physical exercise with activity under short-term loads of maximal intensity has induced a rise of the capacity of oxidative muscles to utilise endogenous and exogenous carbohydrate and lipid reserves.     

Effect of hepatic vagotomy on postexercise substrate levels in food-restricted rats

The metabolic effects of a selective hepatic vagotomy (HV) were investigated at rest and immediately after a 50-min exercise period (26 m/min, 0% grade) in rats subjected to an overnight 50% food restriction. This dietary restriction reduced liver glycogen content to 50% of normal resting concentrations (2.2-2.8 g/100 g). No significant differences between HV and sham-operated rats were found in resting and exercising beta-hydroxybutyrate, glucose, glycerol, and insulin concentrations. Postexercise liver glycogen concentrations were reduced to approximately 1.0 g/100 g in both HV and sham-operated groups. This decrease was associated with significantly (P less than 0.01) lower postexercise glycogen levels in the soleus muscle of HV rats (2.6 times) along with higher plasma free fatty acid concentrations (P less than 0.01). These data provide evidence that HV combined with a progressive decrease in liver glycogen content may influence substrate regulation during exercise. They also support the concept of the existence of hepatic glucoreceptors responsive to a decrease in liver glycogen content.     

Mitochondrial ATP-sensitive K channels as redox signals to liver mitochondria in response to hypertriglyceridemia

We have recently demonstrated that hypertriglyceridemic (HTG) mice present both elevated body metabolic rates and mild mitochondrial uncoupling in the liver owing to stimulated activity of the ATP-sensitive potassium channel (mitoK_ATP). Because lipid excess normally leads to cell redox imbalance, we examined the hepatic oxidative status in this model. Cell redox imbalance was evidenced by increased total levels of carbonylated proteins, malondialdehydes, and GSSG/GSH ratios in HTG livers compared to wild type. In addition, the activities of the extramitochondrial enzymes NADPH oxidase and xanthine oxidase were elevated in HTG livers. In contrast, Mn-superoxide dismutase activity and content, a mitochondrial matrix marker, were significantly decreased in HTG livers. Isolated HTG liver mitochondria presented lower rates of H₂O₂ production, which were reversed by mitoK_ATP antagonists. In vivo antioxidant treatment with N-acetylcysteine decreased both mitoK_ATP activity and metabolic rates in HTG mice. These data indicate that high levels of triglycerides increase reactive oxygen generation by extramitochondrial enzymes that promote mitoK_ATP activation. The mild uncoupling mediated by mitoK_ATP increases metabolic rates and protects mitochondria against oxidative damage. Therefore, a biological role for mitoK_ATP as a redox sensor is shown here for the first time in an in vivo model of systemic and cellular lipid excess.     

Exercise ameliorates insulin resistance via regulating TGFβ-activated kinase 1 (TAK1)-mediated insulin signaling in liver of high-fat diet-induced obese rats

Exercise is an effective therapy for insulin resistance. However, the underlying mechanism remains to be elucidated. Previous research demonstrated that TGFβ-activated kinase 1 (TAK1)-dependent signaling plays a crucial character in hepatic insulin resistance. Hepatic ubiquitin specific protease 4 (USP4), USP18, and dual-specificity phosphatases 14 (DUSP14) can suppress TAK1 phosphorylation, besides tumor necrosis factor receptor-associated factor 3 (TRAF3) and tripartite motif 8 (TRIM8) promote its phosphorylation. In this study, we tried to verify our hypothesis that exercise improves insulin resistance in high-fat diet (HFD)-induced obese (DIO) rats via regulating the TAK1 dependent signaling and TAK1 regulators in liver. Forty male Sprague–Dawley rats were randomized into four groups (n = 10): standard diet and sedentary as normal control; fed on HFD and DIO-sedentary; fed on HFD and DIO-chronic exercise; and fed on HFD and DIO-acute exercise. HFD feeding resulted in increased body weight, visceral fat mass, serum FFAs and hepatic lipid deposition, but decreased hepatic glycogen content and insulin sensitivity. Moreover, hepatic TRAF3 and TRIM8 protein levels increased, whereas USP4, USP18, and DUSP14 protein levels were decreased under obese status, which resulted in enhanced TAK1 phosphorylation and impaired insulin signaling. Exercise training, containing chronic and acute mode, both ameliorated insulin resistance. Meanwhile, decreased TAK1, c-Jun N-terminal kinase 1 (JNK1), and insulin receptor substrate 1 (IRS1) phosphorylation enhanced Akt phosphorylation in liver. Moreover, exercise enhanced USP4 and DUSP14 protein levels, whereas decreased TRIM8 protein levels in obese rats’ liver. These results showed that exercise triggered a crucial modulation in TAK1-dependent signaling and its regulators in obese rats’ liver, and distinct improvement in insulin sensitivity, which provide new insights into the mechanism by which physical exercise improves insulin resistance.     

Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism

Fatty liver is known as the initial stage in nonalcoholic fatty liver disease. Epidemiological studies have shown that regular exercise prevents accumulation of hepatic lipids, although the underlying mechanism is unclear. The purpose of this study was to investigate the effect of exercise on fatty liver associated with hepatic lipid metabolism. KK/Ta mice (6 weeks old) were divided into sedentary and exercise groups and compared with sedentary Balb/c mice. All the mice were fed a high-sucrose diet for 12 weeks. The KK/Ta mice in the exercise group performed a treadmill running exercise at 20 m/min for 30 min (3 times per week). Twelve weeks of regular exercise suppressed the accumulation of lipid in the liver, along with reduction in the level of lipid in the plasma. The levels of carnitine palmitoyl transferase II, acyl-coenzyme A dehydrogenase, and trifunctional enzyme, which are rate-limiting enzymes in fatty acid oxidation in the liver, were elevated by exercise. In addition, the expression of fatty acid synthase, a key lipogenetic enzyme, was reduced by exercise. Furthermore, regular exercise decreased the expression of heat shock protein 47, a marker of hepatic fibrosis, in the liver. Our results suggest that regular exercise prevents fatty liver via improvement of hepatic lipid metabolism.     

Differential action of hepatic sympathetic neuropeptides: metabolic action of galanin, vascular action of NPY

Activation of hepatic nerves increases both hepatic glucose production (HGP) and hepatic arterial vasoconstriction, the latter best described by a decrease of hepatic arterial conductance (HAC). Because activation of canine hepatic nerves releases the neuropeptides galanin and neuropeptide Y (NPY) as well as the classical neurotransmitter norepinephrine (NE), we sought to determine the relative role of these neuropeptides vs. norepinephrine in mediating metabolic and vascular responses of the liver. We studied the effects of local exogenous infusions of galanin and NPY on HGP and HAC to predict the metabolic and vascular function of endogenously released neuropeptide. Galanin (n = 8) or NPY (n = 4) was infused with and without NE directly into the common hepatic artery of halothane-anesthetized dogs, and we measured changes in HGP and HAC. A low dose of exogenous galanin infused directly into the hepatic artery potentiated the HGP response to NE yet had little effect on HGP when infused alone. The same dose of galanin infused into a peripheral vein (n = 8) did not potentiate the HGP response to NE, suggesting that the locally infused galanin acted directly on the liver to modulate NE's metabolic action. In contrast, a large dose of exogenous NPY failed to influence HGP when infused either alone or in combination with NE. Finally, NPY, but not galanin, tended to decrease HAC when infused alone; neither neuropeptide potentiated the HAC response to NE. Therefore, both hepatic neuropeptides may contribute to the action of sympathetic nerves on liver metabolism and blood flow. It is likely that endogenous hepatic galanin acts directly on the liver to selectively modulate norepinephrine's metabolic action, whereas endogenous hepatic NPY acts independently of NE to cause vasoconstriction.     

Hypophysectomy does not alter the acinar zonation of gluconeogenesis or the mitochondrial redox state in rat liver.

The biochemical and functional heterogeneity of hepatocytes in different zones of the liver acinus may be related to the concentrations of hormones within the liver acinus. We examined the effects of hypophysectomy, which causes marked changes in plasma hormone levels and in activities of hepatic enzymes that are normally heterogeneously distributed, on the degree of metabolic zonation within the liver acinus. In hypophysectomized rats the activity of alanine aminotransferase was increased, but its normal zonation (predominance in the periportal zone) was preserved. The activity in cultured periportal and perivenous hepatocytes was increased by dexamethasone, but not by glucagon. Periportal hepatocytes from hypophysectomized rats expressed higher rates of gluconeogenesis in culture than did perivenous hepatocytes, irrespective of the absence or presence of dexamethasone, glucagon or insulin. Similar differences in rates of ketogenesis and in the mitochondrial redox state in response to glucagon were observed between periportal and perivenous hepatocytes from hypophysectomized rats as between cell populations from normal rats. Although hypophysectomy causes marked changes in hepatic enzyme activities, it does not alter the degree of zonation of alanine aminotransferase, gluconeogenesis or the mitochondrial redox state within the liver acinus.     

有氧运动对高脂饮食小鼠肝脏中CLK2蛋白表达的影响

目的: 探讨有氧运动对高脂饮食小鼠肝脏中Cdc2 激酶(CLK2)蛋白表达及肝脏脂肪含量的影响。方法: 雄性C57/BL6小鼠经正常饮食或高脂饮食16周后,分为正常饮食组、高脂饮食组和高脂饮食+运动组(8周有氧运动),每组10只小鼠。采用免疫印迹方法比较各组小鼠肝脏CLK2蛋白表达;采用油红O染色法比较各组小鼠肝脏脂肪含量;采用实时定量PCR方法比较各组小鼠脂肪代谢相关基因。结果:与正常饮食组小鼠相比,高脂饮食小鼠表现出胰岛素抵抗,肝脏CLK2蛋白含量增加,以及肝脏脂肪积累增加。然而有氧运动可改善高脂饮食小鼠胰岛素抵抗状态,并抑制肝脏中CLK2蛋白增加。结论:有氧运动可降低高脂饮食小鼠肝脏中CLK2蛋白表达,而改善肥胖小鼠肝脏脂肪堆积及代谢紊乱。