Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight contro

Energy expenditure, physical activity and body-weight control

Regular physical exercise and endurance training are associated with low body weight and low body fat mass. The relationship between exercise and body-weight control is complex and incompletely understood. Regular exercise may decrease energy balance through an increase in energy expenditure or an increase in fat oxidation. It may also contribute to weight loss by modulating nutrient intake. An intriguing question that remains unresolved is whether changes in nutrient intake or body composition secondarily affect spontaneous physical activity. If this were the case, physical activity would represent a major adaptative mechanism for body-weight control

Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes

Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (Ra) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro

Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors

Ripglut1;glut2-/- mice have no endogenous glucose transporter type 2 (glut2) gene expression but rescue glucose-regulated insulin secretion. Control of glucagon plasma levels is, however, abnormal, with fed hyperglucagonemia and insensitivity to physiological hypo- or hyperglycemia, indicating that GLUT2-dependent sensors control glucagon secretion. Here, we evaluated whether these sensors were located centrally and whether GLUT2 was expressed in glial cells or in neurons. We showed that ripglut1;glut2-/- mice failed to increase plasma glucagon levels following glucoprivation induced either by i.p. or intracerebroventricular 2-deoxy-D-glucose injections. This was accompanied by failure of 2-deoxy-D-glucose injections to activate c-Fos-like immunoreactivity in the nucleus of the tractus solitarius and the dorsal motor nucleus of the vagus. When glut2 was expressed by transgenesis in glial cells but not in neurons of ripglut1;glut2-/- mice, stimulated glucagon secretion was restored as was c-Fos-like immunoreactive labeling in the brainstem. When ripglut1;glut2-/- mice were backcrossed into the C57BL/6 genetic background, fed plasma glucagon levels were also elevated due to abnormal autonomic input to the alpha cells; glucagon secretion was, however, stimulated by hypoglycemic stimuli to levels similar to those in control mice. These studies identify the existence of central glucose sensors requiring glut2 expression in glial cells and therefore functional coupling between glial cells and neurons. These sensors may be activated at different glycemic levels depending on the genetic background

Role of metabolically active hormones in the insulin resistance associated with short-term glucocorticoid treatment

BACKGROUND: The mechanisms by which glucocorticoid therapy promotes obesity and insulin resistance are incompletely characterized. Modulations of the metabolically active hormones, tumour necrosis factor alpha (TNF alpha), ghrelin, leptin and adiponectin are all implicated in the development of these cardiovascular risk factors. Little is known about the effects of short-term glucocorticoid treatment on levels of these hormones. RESEARCH METHODS AND PROCEDURES: Using a blinded, placebo-controlled approach, we randomised 25 healthy men (mean (SD) age: 24.2 (5.4) years) to 5 days of treatment with either placebo or oral dexamethasone 3 mg twice daily. Fasting plasma TNFα, ghrelin, leptin and adiponectin were measured before and after treatment. RESULTS: Mean changes in all hormones were no different between treatment arms, despite dexamethasone-related increases in body weight, blood pressure, HDL cholesterol and insulin. Changes in calculated indices of insulin sensitivity (HOMA-S, insulin sensitivity index) were strongly related to dexamethasone treatment (p < 0.001). DISCUSSION: Our data do not support a role for TNF alpha, ghrelin, leptin or adiponectin in the insulin resistance associated with short-term glucocorticoid treatment

Women Have Higher Protein Content of β-Oxidation Enzymes in Skeletal Muscle than Men

It is well recognized that compared with men, women have better ultra-endurance capacity, oxidize more fat during endurance exercise, and are more resistant to fat oxidation defects i.e. diet-induced insulin resistance. Several groups have shown that the mRNA and protein transcribed and translated from genes related to transport of fatty acids into the muscle are greater in women than men; however, the mechanism(s) for the observed sex differences in fat oxidation remains to be determined. Muscle biopsies from the vastus lateralis were obtained from moderately active men (N = 12) and women (N = 11) at rest to examine mRNA and protein content of genes involved in lipid oxidation. Our results show that women have significantly higher protein content for tri-functional protein alpha (TFPα), very long chain acyl-CoA dehydrogenase (VLCAD), and medium chain acyl-CoA dehydrogenase (MCAD) (P<0.05). There was no significant sex difference in the expression of short-chain hydroxyacyl-CoA dehydrogenase (SCHAD), or peroxisome proliferator activated receptor alpha (PPARα), or PPARγ, genes potentially involved in the transcriptional regulation of lipid metabolism. In conclusion, women have more protein content of the major enzymes involved in long and medium chain fatty acid oxidation which could account for the observed differences in fat oxidation during exercise

Microdialysis in the intensive care unit: a novel tool for clinical investigation or monitoring?

Microdialysis is a minimally invasive tool that allows us to gain insight into metabolism at the tissue level. In human investigations, it can be safely performed in the brain (neurosurgical patients), skeletal muscle and adipose tissue. Basically, the technique allows interstitial concentrations of small solutes to be evaluated. Several limitations of the method and possible ways to circumvent them are indicated. Recent technical developments are reviewed. At present, this method is rarely used in metabolic monitoring of critically ill patients, but its potential applications are highlighted

Stress and metabolism.

Obesity, lipid disorders, type 2 diabetes, high blood pressure and coronary heart disease are frequently encountered in wealthy populations. All these disorders frequently occur as clusters, constituting the metabolic syndrome. It is currently admitted that insulin resistance plays a central role in the pathogenesis of this syndrome. Stress responses include activation of the sympathetic nervous system and stimulation of epinephrine and cortisol release. These hormones may over the long term reduce insulin sensitivity. Cortisol may also favour the development of central obesity. In healthy individuals, mental stress increases heart rate, but simultaneously decreases vascular resistance in skeletal muscle. This results in a moderate increase in blood pressure, and an acute increase in insulin-mediated glucose disposal. In obese patients, mental stress elicits responses which differ widely from those of healthy individuals. While mental stress enhances catecholamine-mediated energy expenditure in obese patients to the same extent as in lean subjects, it fails to decrease systemic vascular resistance due to endothelial dysfunction. This leads to enhanced blood pressure responses and the absence of stimulation of glucose disposal in obese subjects during mental stress. It can be hypothesized that repeated professional or social stress may activate the sympathoadrenal system, resulting in high cortisol levels, stimulation of the sympathetic nervous system, and epinephrine secretion. All these factors may eventually lead to the development of central obesity and insulin resistance. Furthermore, the blood pressure responses to mental stress may be enhanced in insulin-resistant individuals, favouring the development of vascular complications

Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans

The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P &lt;.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased