Metabolic disruptions induced by reduced ambulatory activity in free-living humans

2011 ◽  
Vol 111 (4) ◽  
pp. 1218-1224 ◽  
Author(s):  
John P. Thyfault ◽  
Rikke Krogh-Madsen
Keyword(s):  
Insulin Resistance ◽  
Physical Inactivity ◽  
Direct Evidence ◽  
Bed Rest ◽  
Endurance Athletes ◽  
Central Adiposity ◽  
Ambulatory Activity ◽  
Free Living ◽  
Metabolic Outcomes ◽  
Acute Responses

Physical inactivity likely plays a role in the development of insulin resistance and obesity; however, direct evidence is minimal and mechanisms of action remain unknown. Studying metabolic outcomes that occur after transitioning from higher to lower levels of physical activity is the best tool to answer these questions. Previous studies have successfully used more extreme models of inactivity, including bed rest, or the cessation of exercise in highly trained endurance athletes, to provide novel findings. However, these models do not accurately reflect the type of inactivity experienced by a large majority of the population. Recent studies have used a more applicable model in which active (∼10,000 steps/day), healthy young controls are asked to transition to an inactive lifestyle (∼1,500 steps/day) for a 14-day period. The transition to inactivity resulted in reduced insulin sensitivity and increased central adiposity. This review will discuss the outcomes of these studies, their implications for the cause/effect relationship between central adiposity and insulin resistance, and provide rationale for why inactivity induces these factors. In addition, the experimental challenges of directly linking acute responses to inactivity to chronic disease will also be discussed.

scholarly journals The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers

2016 ◽  
Vol 120 (6) ◽  
pp. 608-614 ◽  
Author(s):  
Signe Tellerup Nielsen ◽  
Nina Majlund Harder-Lauridsen ◽  
Fabiana Braga Benatti ◽  
Anne-Sophie Wedell-Neergaard ◽  
Mark Preben Lyngbæk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Physical Inactivity ◽  
Insulin Response ◽  
Bed Rest ◽  
Fat Free Mass ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Intravenous Glucose ◽  
C Peptide

Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect ( P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect.

Insulin resistance induced by physical inactivity is associated with multiple transcriptional changes in skeletal muscle in young men

2010 ◽  
Vol 299 (5) ◽  
pp. E752-E763 ◽  
Author(s):  
A. C. Alibegovic ◽  
M. P. Sonne ◽  
L. Højbjerre ◽  
J. Bork-Jensen ◽  
S. Jacobsen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Er Stress ◽  
Mitochondrial Function ◽  
Physical Inactivity ◽  
Young Men ◽  
Bed Rest ◽  
Peroxisome Proliferator ◽  
Gene Expressions ◽  
Expression Of Genes

Physical inactivity is a risk factor for insulin resistance. We examined the effect of 9 days of bed rest on basal and insulin-stimulated expression of genes potentially involved in insulin action by applying hypothesis-generating microarray in parallel with candidate gene real-time PCR approaches in 20 healthy young men. Furthermore, we investigated whether bed rest affected DNA methylation in the promoter region of the peroxisome proliferator-activated receptor-γ coactivator-1α ( PPARGC1A) gene. Subjects were reexamined after 4 wk of retraining. We found that bed rest induced insulin resistance and altered the expression of more than 4,500 genes. These changes were only partly normalized after 4 wk of retraining. Pathway analyses revealed significant downregulation of 34 pathways, predominantly those of genes associated with mitochondrial function, including PPARGC1A. Despite induction of insulin resistance, bed rest resulted in a paradoxically increased response to acute insulin stimulation in the general expression of genes, particularly those involved in inflammation and endoplasmatic reticulum (ER) stress. Furthermore, bed rest changed gene expressions of several insulin resistance and diabetes candidate genes. We also observed a trend toward increased PPARGC1A DNA methylation after bed rest. We conclude that impaired expression of PPARGC1A and other genes involved in mitochondrial function as well as a paradoxically increased response to insulin of genes involved in inflammation and ER stress may contribute to the development of insulin resistance induced by bed rest. Lack of complete normalization of changes after 4 wk of retraining underscores the importance of maintaining a minimum of daily physical activity.

Leptin responses to physical inactivity induced by simulated weightlessness

2000 ◽  
Vol 279 (3) ◽  
pp. R891-R898 ◽  
Author(s):  
Stéphane Blanc ◽  
Sylvie Normand ◽  
Christiane Pachiaudi ◽  
Monique Duvareille ◽  
Claude Gharib
Keyword(s):  
Insulin Resistance ◽  
Growth Hormone ◽  
Energy Intake ◽  
Physical Inactivity ◽  
Bed Rest ◽  
Nonesterified Fatty Acid ◽  
Mass Energy ◽  
Simulated Weightlessness ◽  
Resistance Development ◽  
Glucose Ratio

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males ( n = 8) and on alternating days in females ( n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H2 18O dilution. Energy intake (men 10.5 ± 0.2 MJ/day, women 7.9 ± 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0.050), insulin (men 34%, P= 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.

Physical inactivity as the culprit of metabolic inflexibility: evidence from bed-rest studies

2011 ◽  
Vol 111 (4) ◽  
pp. 1201-1210 ◽  
Author(s):  
Audrey Bergouignan ◽  
Floriane Rudwill ◽  
Chantal Simon ◽  
Stéphane Blanc
Keyword(s):  
Insulin Resistance ◽  
Physical Inactivity ◽  
Metabolic Diseases ◽  
Fiber Type ◽  
Bed Rest ◽  
Sedentary Behaviors ◽  
Lipid Trafficking ◽  
Metabolic Adaptations ◽  
Physiological Adaptations ◽  
Metabolic Inflexibility

Although it is no longer debatable that sedentary behaviors are an actual cause of many metabolic diseases, the physiology of physical inactivity has been poorly investigated for this purpose. Along with microgravity, the physiological adaptations to spaceflights require metabolic adaptations to physical inactivity, and that is exceedingly well-simulated during the ground-based microgravity bed-rest analogs. Bed rest thus represents a unique model to investigate the mechanisms by which physical inactivity leads to the development of current societal chronic diseases. For decades, however, clinicians and physiologists working in space research have worked separately without taking full awareness of potential strong mutual questioning. This review summarizes the data collected over the last 60 years on metabolic adaptations to bed rest in healthy subjects. Our aim is to provide evidence that supports the hypothesis that physical inactivity per se is one of the primary causes in the development of metabolic inflexibility. This evidence will focus on four main tenants of metabolic inflexiblity: 1) insulin resistance, 2) impaired lipid trafficking and hyperlipidemia, 3) a shift in substrate use toward glucose, and 4) a shift in muscle fiber type and ectopic fat storage. Altogether, this hypothesis places sedentary behaviors upstream on the list of factors involved in metabolic inflexibility, which is considered to be a primary impairment in several metabolic disorders such as obesity, insulin resistance, and type 2 diabetes mellitus.

scholarly journals Twenty-eight-day bed rest with hypercortisolemia induces peripheral insulin resistance and increases intramuscular triglycerides

Metabolism ◽  
2010 ◽  
Vol 59 (5) ◽  
pp. 703-710 ◽  
Author(s):  
Melanie G. Cree ◽  
Douglas Paddon-Jones ◽  
Bradley R. Newcomer ◽  
Ola Ronsen ◽  
Asle Aarsland ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Bed Rest ◽  
Peripheral Insulin Resistance

scholarly journals Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure

2011 ◽  
Vol 210 (3) ◽  
pp. 349-359 ◽  
Author(s):  
J L Nobre ◽  
P C Lisboa ◽  
A P Santos-Silva ◽  
N S Lima ◽  
A C Manhães ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Leptin Receptor ◽  
Calcium Supplementation ◽  
Dietary Calcium ◽  
Standard Diet ◽  
Adult Offspring ◽  
Nicotine Exposure ◽  
Central Adiposity ◽  
Metabolism Regulation ◽  
The Metabolic Syndrome

Obesity is a worldwide epidemic. Calcium influences energy metabolism regulation, causing body weight loss. Because maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance (IR), and hypothyroidism, we decided to evaluate the possible effect of dietary calcium supplementation on these endocrine dysfunctions in this experimental model. Osmotic minipumps containing nicotine solution (N: 6 mg/kg per day for 14 days) or saline (C) were s.c. implanted in lactating rats 2 days after giving birth (P2). At P120, N and C offspring were subdivided into four groups: 1) C – standard diet; 2) C with calcium supplementation (CCa, 10 g calcium carbonate/kg rat chow); 3) N – standard diet; and 4) N with calcium supplementation (NCa). Rats were killed at P180. As expected, N offspring showed higher visceral and total body fat, hyperleptinemia, lower hypothalamus leptin receptor (OB-R) content, hyperinsulinemia, and higher IR index. Also, higher tyrosine hydroxylase (TH) expression (+51%), catecholamine content (+37%), and serum 25-hydroxyvitamin D3(+76%) were observed in N offspring. Dietary calcium supplementation reversed adiposity, hyperleptinemia, OB-R underexpression, IR, TH overexpression, and vitamin D. However, this supplementation did not reverse hypothyroidism. In NCa offspring,Sirt1mRNA was lower in visceral fat (−37%) and higher in liver (+42%). In conclusion, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in adult offspring programed by maternal nicotine exposure during lactation. It is conceivable that the reduction in fat massper se, induced by calcium therapy, is the main mechanism that leads to the increment of insulin action.

scholarly journals Premature small for gestational age infants fed an exclusive human milk-based diet achieve catch-up growth without metabolic consequences at 2 years of age

2018 ◽  
Vol 104 (3) ◽  
pp. F242-F247 ◽  
Author(s):  
Chonnikant Visuthranukul ◽  
Steven A Abrams ◽  
Keli M Hawthorne ◽  
Joseph L Hagan ◽  
Amy B Hair
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Birth Weight ◽  
Human Milk ◽  
Premature Infants ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Insulin Level ◽  
Metabolic Outcomes ◽  
Catch Up

ObjectiveTo compare postdischarge growth, adiposity and metabolic outcomes of appropriate for gestational age (AGA) versus small for gestational age (SGA) premature infants fed an exclusive human milk (HM)-based diet in the neonatal intensive care unit.DesignPremature infants (birth weight ≤1250 g) fed an exclusive HM-based diet were examined at 12–15 months corrected gestational age (CGA) (visit 1) for anthropometrics, serum glucose and non-fasting insulin, and at 18–22 months CGA (visit 2) for body composition by dual-energy X-ray absorptiometry.ResultsOf 51 children, 33 were AGA and 18 were SGA at birth. The SGA group had weight gain (g/day) equal to AGA group during the follow-up period. SGA had a significantly greater body mass index (BMI) z-score gain from visit 1 to visit 2 (0.25±1.10 vs −0.21±0.84, p=0.02) reflecting catch-up growth. There were no significant differences in total fat mass (FM) and trunk FM between groups. SGA had significantly lower insulin level (5.0±3.7 vs 17.3±15.1 µU/mL, p=0.02) and homeostatic model of assessment-insulin resistance (1.1±0.9 vs 4.3±4.1, p=0.02). Although regional trunk FM correlated with insulin levels in SGA (r=0.893, p=0.04), they had lower insulin level compared with AGA and no difference in adiposity.ConclusionsSGA premature infants who received an exclusive HM-based diet exhibited greater catch-up growth without increased adiposity or elevated insulin resistance compared with AGA at 2 years of age. An exclusive HM-based diet may improve long-term body composition and metabolic outcomes of premature infants with ≤1250 g birth weight, specifically SGA.

scholarly journals The Apparent Relation between Plasma 25-Hydroxyvitamin D and Insulin Resistance Is Largely Attributable to Central Adiposity in Overweight and Obese Adults

2015 ◽  
Vol 145 (12) ◽  
pp. 2683-2689 ◽  
Author(s):  
Christian S Wright ◽  
Eileen M Weinheimer-Haus ◽  
James C Fleet ◽  
Munro Peacock ◽  
Wayne W Campbell
Keyword(s):  
Insulin Resistance ◽  
Central Adiposity ◽  
Obese Adults ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D

scholarly journals The Higher Plasma Malondialdehyde Concentrations Are Determined by Metabolic Syndrome-Related Glucolipotoxicity

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Fernando Moreto ◽  
Erick P. de Oliveira ◽  
Rodrigo M. Manda ◽  
Roberto C. Burini
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Regression Analysis ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Free Living ◽  
Cross Sectional ◽  
Sugar Intake ◽  
Dietary Sugar ◽  
Plasma Malondialdehyde

This study aimed to elucidate the determinants of higher plasma malondialdehyde (MDA) in free-living adults. In a cross-sectional study we evaluated 148 free-living subjects (54 ± 11 years, 78% women) at high risk for or with metabolic syndrome (MetS). They were assessed by anthropometry and body composition, dietary intake, and clinical and laboratorial analysis. The analysis of plasma MDA was performed by HPLC, and concentration values were used to provide four groups according to percentile distribution. Subjects with higher plasma MDA showed higher prevalence of MetS and higher values of waist circumference (WC), glucose, triglycerides (TG),γ-glutamyltransferase (γ-GT), and higher energy intake. Multiadjusted logistic regression analysis identified as determinants of higher plasma MDA the altered values of WC andγ-GT followed by hypertriglyceridemia, hyperglycemia, insulin resistance, higher dietary sugar-intake, and presence of MetS. In conclusion, the glucolipotoxic state predisposed by the presence of MetS seems to be the major determinant of higher plasma MDA concentrations.

Sign in / Sign up

Export Citation Format

Share Document