Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis.

Background: Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system.

Peroxisome proliferator-activated receptors: a therapeutic target in COPD?

Extrapulmonary pathology significantly impairs clinical outcome in chronic obstructive pulmonary disease (COPD). The peroxisome proliferator-activated receptors (PPARs) are implicated in the regulation of several hallmarks of systemic COPD pathology, including cachexia, decreased oxidative muscle metabolism, oxidative stress and systemic inflammation. Recently, expression of PPARs and related cofactors was shown to be reduced in peripheral skeletal muscle of patients with moderate-to-severe COPD and muscle weakness.

Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake.

Skeletal muscle gene response to exercise depends on nutritional status during and after exercise, but it is unknown whether muscle adaptations to endurance training are affected by nutritional status during training sessions. Therefore, this study investigated the effect of an endurance training program (6 wk, 3 day/wk, 1-2 h, 75% of peak Vo(2)) in moderately active males. They trained in the fasted (F; n = 10) or carbohydrate-fed state (CHO; n = 10) while receiving a standardized diet [65 percent of total energy intake (En) from carbohydrates, 20%En fat, 15%En protein].

Mitochondrial function, content and ROS production in rat skeletal muscle: effect of high-fat feeding.

A high intake of dietary fat has been suggested to diminish mitochondrial functioning in skeletal muscle, possibly attributing to muscular fat accumulation. Here we show however, that an 8-week high-fat dietary intervention did not affect intrinsic functioning of rat skeletal muscle mitochondria assessed by respirometry, neither on a carbohydrate- nor on a lipid-substrate. Interestingly, PPARGC1A protein increased by approximately 2-fold upon high-fat feeding and we observed inconsistent results on different markers of mitochondrial density.

Muscular diacylglycerol metabolism and insulin resistance.

Failure of insulin to elicit an increase in glucose uptake and metabolism in target tissues such as skeletal muscle is a major characteristic of non-insulin dependent type 2 diabetes mellitus. A strong correlation between intramyocellular triacylglycerol concentrations and the severity of insulin resistance has been found and led to the assumption that lipid oversupply to skeletal muscle contributes to reduced insulin action. However, the molecular mechanism that links intramyocellular lipid content with the generation of muscle insulin resistance is still unclear.

Diet and nonalcoholic fatty liver disease.

Purpose Of Review: Nonalcoholic fatty liver disease is a common and serious form of chronic liver disease. It is characterized by lipid accumulation in the liver and is associated with all aspects - and may even be an initiating factor - of the metabolic syndrome. The purpose of this review is to summarize recent findings from human studies on dietary effects on hepatic lipid accumulation.

Muscular mitochondrial dysfunction and type 2 diabetes mellitus.

Purpose Of Review: Muscular mitochondrial dysfunction, leading to the accumulation of fat in skeletal muscle, has been proposed to be involved in the development of type 2 diabetes mellitus. Here, we review human studies that investigated various aspects of mitochondrial function in relation to muscular insulin sensitivity and/or diabetes.

Recent Findings: In-vivo magnetic resonance spectroscopy allows assessment of mitochondrial functionality from adenosine triphosphate flux in the nonexercising state and from phosphocreatine recovery from (sub)maximal exercising.

Loss of 50% of excess weight using a very low energy diet improves insulin-stimulated glucose disposal and skeletal muscle insulin signalling in obese insulin-treated type 2 diabetic patients.

Aims/hypothesis: Both energy restriction (ER) per se and weight loss improve glucose metabolism in obese insulin-treated type 2 diabetic patients. Short-term ER decreases basal endogenous glucose production (EGP) but not glucose disposal. In contrast the blood glucose-lowering mechanism of long-term ER with substantial weight loss has not been fully elucidated.

Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice.

Activation of C5L2, a G-protein-coupled receptor, by acylation-stimulating protein/complement C3adesArg (ASP/C3adesArg) has been shown to stimulate triglyceride (TG) synthesis in both mature adipocytes and preadipocytes. ASP is an adipocyte-derived hormone that acts by increasing diacylglycerol acyltransferase activity and glucose transport. ASP-deficient mice (C3KO, precursor protein) are lean, display delayed postprandial TG clearance, increased food intake, and increased energy expenditure.

Skeletal muscle uncoupling protein-3 restores upon intervention in the prediabetic and diabetic state: implications for diabetes pathogenesis?

Aim: Skeletal muscle uncoupling protein-3 (UCP3) is reduced in type 2 diabetes, and in the pre-diabetic condition of impaired glucose tolerance (IGT). Here we examined whether intervention programs known to improve insulin sensitivity are paralleled by an increase in skeletal muscle UCP3 protein levels.

Methods: Skeletal muscle UCP3 protein content was measured before and after one year of an exercise intervention in muscle biopsies of eight diabetic subjects.

Physical activity and diabetes: current considerations.

The prevalence of diabetes is increasing rapidly. Overeating, leading to obesity and overweight, is often considered the main determinant of this increase. However, evidence is accumulating that physical inactivity may be as important a factor in the development of diabetes as being overweight.

Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD.

Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure.

High-fat diet, muscular lipotoxicity and insulin resistance.

A high dietary fat intake and low physical activity characterize the current Western lifestyle. Dietary fatty acids do not stimulate their own oxidation and a surplus of fat is stored in white adipose tissue, liver, heart and muscle. In these organs intracellular lipids serve as a rapidly-available energy source during, for example, physical activity.

Improved skeletal muscle oxidative enzyme activity and restoration of PGC-1 alpha and PPAR beta/delta gene expression upon rosiglitazone treatment in obese patients with type 2 diabetes mellitus.

Objective: To examine whether rosiglitazone alters gene expression of some key genes involved in mitochondrial biogenesis and oxidative capacity in skeletal muscle of type 2 diabetic patients, and whether this is associated with alterations in skeletal muscle oxidative capacity and lipid content.

Design: measured in muscle biopsies obtained from diabetic patients, before and after 8 weeks of rosiglitazone treatment, and matched controls. Furthermore, whole-body insulin sensitivity and substrate utilization were assessed.

Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects.

Aims/hypothesis: Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls.

Methods: In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.

Eat the meat or feed the meat: protein turnover in remodeling muscle.

Purpose Of Review: The present review outlines the role of muscle protein turnover in muscle remodeling, with emphasis on the effects of nutrition and exercise.

Recent Findings: Progress in our understanding of the pathways signaling and regulating protein synthesis and degradation, and thus protein turnover, in skeletal muscle has been substantial over the past decade. Protein synthesis and degradation jointly allow the active remodeling of skeletal muscle to adapt to changes in mechanical and metabolic demand.

UCP3 in muscle wasting, a role in modulating lipotoxicity?

UCP3 has been postulated to function in the defense against lipid-induced oxidative muscle damage (lipotoxicity). We explored this hypothesis during cachexia in rats (zymosan-induced sepsis), a condition characterized by increased oxidative stress and supply of fatty acids to the muscle. Muscle UCP3 protein content was increased 2, 6 and 11 days after zymosan injection.

Peroxisome proliferator-activated receptor-gamma coactivator-1 and insulin resistance: acute effect of fatty acids.

Aims/hypothesis: Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect of early aberrations in the development of insulin resistance, such as disturbances in fat metabolism, is unknown. We examined whether lipid-induced insulin resistance was associated with downregulation of expression of skeletal muscle genes involved in oxidative metabolism and mitochondrial biogenesis in humans.

Regional variations in intramyocellular lipid concentration correlate with muscle fiber type distribution in rat tibialis anterior muscle.

1H MR spectroscopy (MRS) has proved to be a valuable noninvasive tool to measure intramyocellular lipids (IMCL) in research focused on insulin resistance and type II diabetes in both humans and rodents. An important determinant of IMCL is the muscle fiber type, since oxidative type I fibers can contain up to three times more IMCL than glycolytic type II muscle fibers. Because these different muscle fiber types are inhomogeneously distributed in rodent muscle, in the present study we investigated the distribution of IMCL within the rat tibialis anterior muscle (TA) in vivo using single-voxel 1H MRS along with the muscle fiber distribution in the TA ex vivo determined from immunohistological assays.

Intramyocellular lipid content in human skeletal muscle.

Fat can be stored not only in adipose tissue but also in other tissues such as skeletal muscle. Fat droplets accumulated in skeletal muscle [intramyocellular lipids (IMCLs)] can be quantified by different methods, all with advantages and drawbacks. Here, we briefly review IMCL quantification methods that use biopsy specimens (biochemical quantification, electron microscopy, and histochemistry) and non-invasive alternatives (magnetic resonance spectroscopy, magnetic resonance imaging, and computed tomography).

Short-term training is accompanied by a down regulation of ACC2 mRNA in skeletal muscle.

Recently, we showed that short-term training induced a rapid increase in IMCL whilst insulin sensitivity tended to improve. Here we investigate molecular adaptations accompanying this physiological training-induced accumulation of IMCL. Nine untrained men (age: 23.

Involvement of UCP3 in mild uncoupling and lipotoxicity.

Although vital to life, mitochondria are also the major source of ROS production, which may have unwanted detrimental effects on DNA, RNA and protein structures Therefore, mitochondria must exhibit well-developed mechanisms to regulate its ROS production. One such mechanism might be mild uncoupling of the mitochondrial respiratory chain, thereby lowering the proton gradient across the inner mitochondrial membrane and directly lowering ROS production. Mitochondrial uncoupling proteins have been shown to possess mild uncoupling activity and may therefore be important regulator of mitochondrial ROS production.

The effect of high-fat feeding on intramuscular lipid and lipid peroxidation levels in UCP3-ablated mice.

Uncoupling protein-3 (UCP3) has been suggested to protect against lipid-induced oxidative damage. Therefore, we studied intramuscular lipid peroxide levels and high-fat diet induced alterations in muscle lipid metabolism of UCP3-ablated mice. UCP3-/- mice showed approximately 3-fold higher levels of intramuscular lipid peroxides upon standard chow feeding, compared to wild-type littermates.

Intramyocellular lipid content and molecular adaptations in response to a 1-week high-fat diet.

Objective: To investigate molecular adaptations that accompany the elevation of intramyocellular lipid (IMCL) content on a high-fat (HF) diet for 1 week.

Research Methods And Procedures: Ten subjects consumed a normal-fat (NF) diet for 1 week, followed by an HF diet for another week. After both dietary periods, we determined the IMCL content by proton magnetic resonance spectroscopy in the vastus lateralis muscle and quantified changes in gene expression, protein content, and activity in biopsy samples.