Maurice Harold Laughlin

• PhD
• Chair at University of Missouri

Regular aerobic exercise (RAEX) elicits several positive adaptations in all organs and tissues of the body, culminating in improved health and well-being. Indeed, in over half a century, many studies have shown the benefit of RAEX on cardiovascular outcome in terms of morbidity and mortality. RAEX elicits a wide range of functional and structural a...

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we...

Duchenne muscular dystrophy (DMD) is a muscle wasting disease caused by dystrophin deficiency. Vascular dysfunction has been suggested as an underlying pathogenic mechanism in DMD. However, this has not been thoroughly studied in a large animal model. Here we investigated structural and functional changes in the vascular smooth muscle and endotheli...

Dysregulated mitochondrial quality control leads to mitochondrial functional impairments that are central to the development and progression of hepatic steatosis to steatohepatitis (NASH). Here we identify hepatocellular localized endothelial nitric oxide synthase (eNOS) as a novel master regulator of mitochondrial quality control. Mice lacking eNO...

We present the hypothesis that exercise-induced hyperemia, perhaps through vascular shear stress, represents an important factor responsible for the effects of physical activity (PA) on vascular insulin sensitivity. Specifically, we postulate PA involving the greatest amount of skeletal muscle mass and the greatest central neural recruitment maximi...

Swine with familial hypercholesterolemia (FH) exhibit attenuated exercise‐induced systemic vasodilation that is restored by phosphodiesterase 5 (PDE5) inhibition. Whether the impacts of FH and PDE5 inhibition to impair and restore, respectively, exercise‐induced vasodilation results from tissue‐specific or generalized effects remains unclear. Thus,...

Prospective, cohort studies in humans demonstrate that moderate to high levels of physical activity reduce both morbidity and mortality of coronary heart disease (CHD) including a decreased progression and/or regression of CHD with life‐style modification which includes exercise. However, a thorough review of both human and animal literature reveal...

Objective Swine with familial hypercholesterolemia (FH) exhibit attenuated exercise‐induced systemic vasodilation that is restored by phosphodiesterase 5 (PDE5) inhibition. Whether the impacts of FH and PDE5 inhibition to impair and restore, respectively, exercise‐induced vasodilation results from tissue‐specific or generalized effects remains uncl...

Vascular remodelling plays an important role in the adaptation of the athlete to increased exercise duration and intensity. Endurance exercise improves endothelium-dependent flow-mediated vasodilation and leads to increases in conduit artery lumen diameter after regular exercise, typically in the trained limb. These changes result in a reduced vasc...

Human studies demonstrate that physical activity reduces both morbidity and mortality of coronary heart disease (CHD) including decreased progression and/or regression of CHD with life‐style modification which includes exercise. However, evidence supporting an intrinsic, direct effect of exercise in attenuating the development of CHD is equivocal....

Vascular dementia accounts for ~35% of all forms of dementia in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. HFpEF comprises 50% of all HF cases and is clinically characterized by comorbidities including aging, obesity, hypertension, and type 2 diabetes (T2D), with increased prevale...

We have previously reported coronary vascular dysfunction mediated by the large conductance Ca ²⁺ ‐activated K ⁺ channel (BK Ca ) in swine models of pressure overload‐induced heart failure (HF). The purpose of this study was to determine whether the observed dysfunction is due to a change in the protein level or cellular location of the pore‐formin...

Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on BKCachannel-mediated coronary vascular function in heart failure. We hypothesized chronic interval ex...

Background: Impaired microvascular insulin signaling may develop prior to overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signa...

Background Postmenopausal women represent the largest cohort of patients with heart failure with preserved ejection fraction, and vascular dementia represents the most common form of dementia in patients with heart failure with preserved ejection fraction. Therefore, we tested the hypotheses that the combination of cardiac pressure overload (aortic...

On the 400th anniversary of Harvey?s Lumleian lectures, this review focuses on ?hemodynamic? forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone vi...

This study tested the hypotheses that obesity-induced decrements in insulin-stimulated cerebrovascular vasodilation would be normalized with acute endothelin-1a receptor antagonism, and treatment with a physical activity intervention restores vasoreactivity to insulin through augmented nitric oxide synthase (NOS)-dependent dilation. Otsuka Long-Eva...

We examined the effects of metformin, a commonly used antidiabetic drug, on gene expression in multiple arteries. Specifically, transcriptional profiles of feed arteries and second branch order arterioles in the soleus, gastrocnemius, and diaphragm muscles as well as aortic endothelial scrapes were examined from obese insulin-resistant Otsuka Long-...

Objective: EXT-induced arteriolar adaptations in skeletal muscle are heterogeneous because of spatial variations in muscle fiber type composition and fiber recruitment patterns during exercise. The purpose of this report is to summarize a series of experiments conducted to test the hypothesis that changes in vascular gene expression are signaled b...

Accelerated development of coronary atherosclerosis is a defining characteristic of familial hypercholesterolemia (FH). However, the recent data highlight a significant cardiovascular risk prior to the development of critical coronary stenosis. We, therefore, examined the hypothesis that FH produces coronary microvascular dysfunction and impairs co...

Hyperphagic Otsuka Long-Evans Tokushima fatty (OLETF) rats develop obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD), but lifestyle modifications, such as caloric restriction (CR), can prevent these conditions. We sought to determine if prior CR had protective effects on metabolic health and NAFLD development following a 4-w...

Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces br...

Background: Cognitive impairment in the setting of heart failure with preserved ejection fraction remains poorly understood. Using aortic-banded miniature swine displaying pathological features of human heart failure with preserved ejection fraction, we tested the hypothesis that increased carotid artery stiffness and altered carotid blood flow co...

Key points: Physiologically relevant rodent models of NASH that resemble the human condition are limited. Exercise training and energy restriction are first line recommendations for the treatment of NASH. Hyperphagic OLETF rats fed a Western diet high in fat, sucrose, and cholesterol for 24 weeks developed a severe NASH with fibrosis phenotype. Mo...

INTRODUCTION We previously have shown that loss of hepatic endothelial nitric oxide synthase (eNOS) activity is linked to nonalcoholic steatohepatitis (NASH) development and progression. In addition, whole‐body eNOS −/− mice are susceptible to western diet induced hepatic mitochondrial dysfunction and NASH. However, it is unclear whether eNOS is ex...

INTRODUCTION Consistent with the well characterized role for endothelial nitric oxide synthase (eNOS) to stimulate mitochondrial biogenesis, we have previously demonstrated that eNOS knockout ( eNOS −/− ) mice have reduced hepatic expression of PGC1α and TFAM in association with reduced mitochondrial respiratory capacity in western diet‐induced non...

Insulin stimulates resistance artery vasodilation in skeletal muscle and the brain. Type 2 diabetes (T2D) attenuates insulin‐induced vasodilation in skeletal muscle arteries, but whether this adaptation occurs in the cerebrovasculature and is related to impaired cognition remains to be elucidated. This study tested the hypothesis that cognition and...

Introduction Our group has previously shown that obesity decreases capillary density in skeletal muscle. Here, we tested the hypothesis that decreased capillary density in obesity is the result of increased activity of the insulin growth factor II receptor (IGF2R) in degrading urokinase‐plasminogen receptor (uPAR), activating transforming growth fa...

The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female health...

Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25Lmin-1. In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increas...

Background Although acute elevation in retrograde shear rate (SR) impairs endothelial function, no previous study has explored the effect of prolonged elevation of retrograde SR on conduit artery vascular function. We examined the effect of 2‐weeks elevation of retrograde SR on brachial artery endothelial function in young and in older men. Method...

Using next generation, transcriptome-wide, RNA sequencing (RNA-Seq) technology we assessed the effects of exercise training on transcriptional profiles in skeletal muscle arterioles isolated from the soleus and gastrocnemius muscles of Otsuka Long Evans Tokushima Fatty (OLETF) rats that underwent an endurance exercise training program (EX; n=13), i...

We employed next generation, transcriptome-wide, RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the d...

Low-intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascul...

Weight loss is recommended for patients with nonalcoholic fatty liver disease (NAFLD), while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of weight loss and metformin in the treatment of NAFLD is unclear. We assessed the effects of metformin, caloric restriction, and their combination on NAFLD in diabe...

Increased levels of physical activity are asso- ciated with reduced cardiovascular disease (CVD) risk and mortality in obesity and diabetes. Available evidence suggests that local factors, including local hemody-namics, account for a significant portion of this CVD protection, and numerous studies have interrogated the therapeutic benefit of physic...

Nitric oxide produced by endothelial nitric oxide synthase (eNOS) can influence mitochondrial biogenesis and electron transport chain activity. Hepatic mitochondrial dysfunction is a hallmark feature of nonalcoholic fatty liver disease (NAFLD), yet the underlying mechanisms remain elusive. Here, we tested the hypothesis that eNOS plays an important...

The left anterior descending (LAD, interventricular) coronary artery provides the blood supply to the mid-region of the heart and is a major site of vessel stenosis. Changes in LAD function can have major effects on heart function. In this report, we examined the effect of electron simulated solar particle event (eSPE) radiation on LAD function in...

The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is a serious health concern, but the underlying mechanisms remain unclear. To address this, we hypothesized that chronic inhibition of NO synthase (NOS) via Nω-nitro-L-arginine methyl ester (L-NAME) would intensify liver injury in a rat model of obesi...

Rapid onset vasodilation (ROV) following single muscle contractions has been examined in the forearm of humans, but has not yet been characterized in the leg. Given known vascular differences between the arm and leg, we sought to characterize ROV following single muscle contractions in the leg. Sixteen healthy men performed random ordered single co...

We used next-generation RNA sequencing (RNA-Seq) technology to identify genes whose expression is consistently affected by obesity across multiple arteries. Specifically, transcriptional profiles of the iliac artery as well as the feed artery, first, second, and third branch order arterioles in the soleus, gastrocnemius and diaphragm muscles from o...

Purpose. Coronary microvascular dysfunction is increasingly recognized as a contributor to myocardial ischemia in patients with coronary artery disease. Here we investigated perturbations in the regulation of coronary resistance vessel tone and myocardial oxygen balance at rest and during treadmill exercise, in a porcine model of familial hyperchol...

Background: There is increasing use of high-intensity interval-type exercise training in the management of many lifestyle-related diseases. Purpose: This study aimed to test the hypothesis that vigorous-intensity interval exercise is as effective as traditional moderate-intensity aerobic exercise training for nonalcoholic fatty liver disease (NA...

Purpose ATP could play an important role in skeletal muscle blood flow regulation by inducing vasodilation via purinergic P2 receptors. This study investigated the role of P2 receptors in exercise hyperemia in miniature swine. Methods We measured regional blood flow with radiolabeled-microsphere technique and systemic hemodynamics before and aft...

We employed next-generation RNA sequencing (RNA-Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from obese Otsuka Long-Evans Tokushim...

The purpose was to test the hypothesis that adipocytes from obese rats would exert pro-atherogenic paracrine effects on cultured endothelial cells compared to adipocytes from lean rats, and that the adverse obesity-associated paracrine effects of adipocytes would be more pronounced in visceral than subcutaneous adipose tissue. Epididymal and subcut...

We employed next generation RNA sequencing (RNA‐Seq) technology to determine the extent to which exercise alters global gene expression in skeletal muscle feed arteries and aortic endothelial cells (AEC) of obese OLETF rats. Transcriptional profiles of the soleus and gasctrocnemius muscle feed arteries (SFA and GFA, respectively) and AEC‐enriched s...

We tested the hypothesis that chronic disruption of constitutive nitric oxide (NO) production via the non‐selective NO synthase (NOS) inhibitor N ω ‐nitro‐L‐arginine methyl ester (L‐NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and nonalcoholic fatty liver disease (NAFLD). Obese Otsuka Long‐Evans Tokushima Fatty...

We employed next generation RNA sequencing (RNA‐Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gasctrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell‐enriched samples from obese Otsuka Long Evans Tokushi...

Weight loss is recommended for nonalcoholic fatty liver disease (NAFLD) patients while metformin may lower liver enzymes in type 2 diabetics. Yet, the efficacy of the combination of treatments on NAFLD is unclear. We sought to assess the effects of metformin, caloric restriction, and the combination on NAFLD in diabetic Otsuka Long‐Evans Tokushima...

The purpose of this study was to determine the magnitude of increased blood flow (BF) to rat adipose tissue depots that is signaled by hyperglycemia. BF was measured in adult SD rats (422±2.6 g, n=6) after 5 hr fasting with stable isotope labeled microshereres. > 4 hr recovery from arterial catheterizing surgery, BF was determined in conscious rats...

Purpose. We tested the hypothesis that nonalcoholic fatty liver disease (NAFLD) is associated with reduced hepatic endothelial nitric oxide synthase (eNOS) activation status via S1177 phosphorylation (p-eNOS) and is prevented by daily voluntary wheel running (VWR). Methods. Hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established...

Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in...

We tested the hypothesis that a decrease in bioavailability of nitric oxide (NO) would result in increased adipose tissue (AT) inflammation. In particular, we utilized the obese Otsuka Long Evans Tokushima Fatty rat model (n = 20) and lean Long Evans Tokushima Otsuka counterparts (n = 20) to determine the extent to which chronic inhibition of NO sy...

Nitric oxide (NO)-induced coronary vasodilation is mediated through production of cyclic guanosine monophosphate (cGMP), and through inhibition of the endothelin-1 (ET) system. We previously demonstrated that phosphodiesterase-5 (PDE5)-mediated cGMP breakdown and ET each exert a vasoconstrictor influence on coronary resistance vessels. However, lit...

Key points Familial hypercholesterolaemia (FH) causes vascular dysfunction involving reduced nitric oxide (NO) bioavailability and limits exercise‐induced vasodilatation in the systemic, but not pulmonary, vasculature. The mechanism(s) underlying blunted exercise‐induced systemic vasodilatation in FH are unclear but may involve enhanced endothelin‐...

Both phosphodiesterase 5 (PDE5) inhibition and endothelin (ET) receptor blockade have been shown to induce pulmonary vasodilation. However, little is known about the effect of combined blockade of these two vasoconstrictor pathways. Since nitric oxide (NO) exerts its pulmonary vasodilator influence via production of cyclic guanosine monophosphate (...

We employed next generation RNA sequencing (RNA-Seq) technology to determine the extent to which exercise training alters global gene expression in skeletal muscle feed arteries and aortic endothelial cells of obese OLETF rats. Transcriptional profiles of the soleus and gasctrocnemius muscle feed arteries (SFA and GFA, respectively) and aortic endo...

In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3-5 mm width coronary EAT (cEAT)...

History of Exercise Physiology brings together leading authorities in the profession to present this unique resource that is certain to become an essential reference for exercise physiology researchers and practitioners. The contributing authors have all made significant contributions to the field, including many examples in which they were part of...

Here we sought to compare the efficacy of combining exercise and metformin for the treatment of type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) in hyperphagic, obese, type 2 diabetic, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats (age 20 wks; hyperglycemic and hyperinsulinemic; n=10/group) were randomly assigned to sedenta...

The capability for externally applied rhythmic limb compressions to improve the outcomes of patients with peripheral artery disease has been recognized for nearly a century. Modern technology has permitted the development of portable and cost-effective intermittent pneumatic compression (IPC) systems to be made readily available for affordable at-h...

New Findings What is the central question of this study? Does endurance exercise training cause anti‐atherogenic effects on the endothelium in a swine model of familial hypercholesterolaemia (FH), and how are these effects distributed across veins, arteries and multiple vascular territories within each system? What is the main finding and its impor...

New Findings What is the central question of this study? Adverse maternal behaviour during pregnancy is well known to have lifelong health consequences for offspring. We asked whether a positive maternal health behaviour may have positive long‐term effects for offspring. Specifically, we investigated whether aerobic maternal exercise improves nitri...

Hypercholesterolemia impairs endothelial function (e.g. the NO- cGMP-phosphodiesterase 5 (PDE5) pathway), limits shear stress induced vasodilation, and is therefore expected to reduce exercise-induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise-induced vasodilation, we compared the effects...

New findings What is the central question of this study? This study investigated the influence of obesity on insulin‐induced vasomotor reactivity in rat skeletal muscle feed arteries. What is the main finding and its importance? Irrespective of obesity, the gastrocnemius feed artery displayed diminished insulin‐induced vasodilatory response compare...

To test the hypothesis that chronic metformin treatment enhances insulin-induced vasodilation in skeletal muscle resistance arteries and arterioles. We assessed the effect of metformin treatment (from 20-32 wks of age) of obese Otsuka Long Evans Tokushima Fatty (OLETF) rats and lean Long Evans Tokushima Otsuka (LETO) rats (300 mg/kg) on insulin-sti...

Dysfunction of the endothelium is proposed as the primary initiator of atherosclerotic peripheral artery disease, which occurs mainly in medium- to large-sized conduit arteries of the lower extremities (e.g., iliac, femoral, popliteal arteries). In this review article, we propose the novel concept that conduit artery endothelial cell phenotype is d...

New findings What is the central question of this study? What are the effects of caloric restriction and chronic exercise on β‐adrenergic and natriuretic peptide receptor genes in visceral adipose tissue of obese rats? What is the main finding and its importance? Physical activity induced increases in natriuretic peptide receptor (NPR) and β‐adrene...

Exercise training elevates circulating irisin and induces the expression of the FNDC5 gene in skeletal muscles of mice. Our objective was to determine whether exercise training also increases FNDC5 protein or mRNA expression in the skeletal muscles of pigs as well as plasma irisin. Castrated male pigs of the Rapacz familial hypercholesterolemic (FH...

The heterogeneous progression of atherosclerotic disease in the peripheral arteries is currently not well understood. In humans, artery specific disease progression is partly attributed to the local hemodynamic environments. However, despite similar hemodynamic environments, porcine brachial arteries are protected while femoral arteries are highly...

We adopted a transcriptome-wide microarray analysis approach to determine the extent to which vascular gene expression is altered as a result of juvenile obesity and identify obesity-responsive mRNAs. We examined transcriptional profiles in the left anterior descending coronary artery (LAD), perivascular fat adjacent to the LAD, and descending thor...

Objectives: This study sought to determine if simvastatin impairs exercise training adaptations. Background: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and i...

Obesity, insulin resistance and the metabolic syndrome (MetS) cause coronary microvascular dysfunction and defects of coronary flow control. Although myriad mechanisms contribute to this dysfunction no study has comprehensively determined MetS‐associated differential coronary vascular gene expression (the coronary transcriptome). Coronary arteriola...

Endurance exercise training (EX) is reported to increase FNDC5 expression in skeletal muscle (SkM) of mice (Nature 481:463, 2012). We tested the hypothesis that EX increases FNDC5 expression in pig SkM. Castrated male Rapacz hypercholesterolemic (FH) and normal Yucatan miniature swine (Y) were divided into EX and unexercised (SED) groups. After 16–...

Exercise and metformin are common therapies for type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). However, it is unclear whether combining therapies offers greater benefit for T2D and NAFLD outcomes. We randomly assigned type 2 diabetic, Otsuka Long‐Evans Tokushima Fatty (OLETF) rats (age 20 wks; n=10/group) to sedentary (SED), SE...

A large body of evidence links decreased and/or oscillatory blood flow and shear to the development of a pro‐atherogenic vascular endothelial phenotype. However, additional human studies are needed to provide more definitive support for this link, as most of the available data come from in vitro experiments and rodent models. To address this, a 220...

Physical activity induced prevention of hepatic steatosis is maintained during short-term (7-day) transitions to an inactive state; however, whether these protective effects are present under longer duration physical inactivity is largely unknown. Here we sought to determine whether previous physical activity had protective effects on hepatic steat...

Perivascular adipose tissue (PVAT) is implicated as a source of pro-atherogenic cytokines. Phenotypic differences in local PVAT depots may contribute to differences in disease susceptibility among arteries and even regions within an artery. It has been proposed that PVAT around the abdominal and thoracic aorta share characteristics of white and bro...

There is strong and consistent evidence from in vitro studies that disturbed blood flow produces a proatherogenic vascular endothelial phenotype. However, data from human studies are lacking. To address this, a 220 mm Hg occlusion cuff was placed on the distal forearm of 10 young, healthy men to induce a localized region of disturbed blood flow in...

Background Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Objective Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterio...

Adipose tissue inflammation plays a role in cardiovascular (CV) and metabolic diseases associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM). The interactive effects of exercise training and metformin, two first-line T2DM treatments, on adipose tissue inflammation are not known. Using the hyperphagic, obese, insulin resist...

Chronic treatment with fibroblast growth factor 21 (FGF-21) favorably improves obesity and nonalcoholic fatty liver disease (NAFLD) outcomes; however, FGF-21 expression is paradoxically elevated in obese conditions. Here, we sought to determine the effects of obesity prevention by daily exercise (EX) vs. caloric restriction (CR) on hepatic FGF-21 i...