Dynamics of Fat Oxidation from Sitting at Rest to Light Exercise in Inactive Young Humans.

Societal erosion of daily life low-level physical activity has had a great influence on the obesity epidemic. Given that low fat oxidation is also a risk factor for obesity, we investigated, in a repeated measures design, the dynamics of fat oxidation from a resting state to a light-intensity leg cycling exercise (0-50 watts) in inactive, healthy young adults. Using indirect calorimetry, energy expenditure and the respiratory quotient (RQ) were assessed in a sitting posture at rest and during a cycling exercise in 35 subjects (20 women). The rate of perceived exhaustion (RPE) was assessed using the Borg Scale. During graded leg cycling, the mean RPE did not exceed values corresponding to the exercise being perceived as 'light'. However, analysis of individual data at 50 watts revealed two distinct subgroups among the subjects: those having RPE values corresponding to the exercise being perceived as 'very light to light' and showing no increase in RQ relative to resting levels, as opposed to an increase in RQ in those who perceived the exercise as being 'somewhat hard to hard' (p < 0.001). Our study in inactive individuals showing that high fat oxidation was maintained during 'light-perceived' physical activity reinforced the potential importance of light physical activity in the prevention of obesity.

Adaptive Thermogenesis Driving Catch-Up Fat Is Associated With Increased Muscle Type 3 and Decreased Hepatic Type 1 Iodothyronine Deiodinase Activities: A Functional and Proteomic Study.

Refeeding after caloric restriction induces weight regain and a disproportionate recovering of fat mass rather than lean mass (catch-up fat) that, in humans, associates with higher risks to develop chronic dysmetabolism. Studies in a well-established rat model of semistarvation-refeeding have reported that catch-up fat associates with hyperinsulinemia, glucose redistribution from skeletal muscle to white adipose tissue and suppressed adaptive thermogenesis sustaining a high efficiency for fat deposition. The skeletal muscle of catch-up fat animals exhibits reduced insulin-stimulated glucose utilization, mitochondrial dysfunction, delayed in vivo contraction-relaxation kinetics, increased proportion of slow fibers and altered local thyroid hormone metabolism, with suggestions of a role for iodothyronine deiodinases. To obtain novel insights into the skeletal muscle response during catch-up fat in this rat model, the functional proteomes of tibialis anterior and soleus muscles, harvested after 2 weeks of caloric restriction and 1 week of refeeding, were studied. Furthermore, to assess the implication of thyroid hormone metabolism in catch-up fat, circulatory thyroid hormones as well as liver type 1 (D1) and liver and skeletal muscle type 3 (D3) iodothyronine deiodinase activities were evaluated. The proteomic profiling of both skeletal muscles indicated catch-up fat-induced alterations, reflecting metabolic and contractile adjustments in soleus muscle and changes in glucose utilization and oxidative stress in tibialis anterior muscle. In response to caloric restriction, D3 activity increased in both liver and skeletal muscle, and persisted only in skeletal muscle upon refeeding. In parallel, liver D1 activity decreased during caloric restriction, and persisted during catch-up fat at a time-point when circulating levels of T4, T3 and rT3 were all restored to those of controls. Thus, during catch-up fat, a local hypothyroidism may occur in liver and skeletal muscle despite systemic euthyroidism. The resulting reduced tissue thyroid hormone bioavailability, likely D1- and D3-dependent in liver and skeletal muscle, respectively, may be part of the adaptive thermogenesis sustaining catch-up fat. These results open new perspectives in understanding the metabolic processes associated with the high efficiency of body fat recovery after caloric restriction, revealing new implications for iodothyronine deiodinases as putative biological brakes contributing in suppressed thermogenesis driving catch-up fat during weight regain.

Countering impaired glucose homeostasis during catch-up growth with essential polyunsaturated fatty acids: is there a major role for improved insulin sensitivity?

BACKGROUND/OBJECTIVES: Catch-up growth, an important risk factor for later obesity and type 2 diabetes, is often characterized by a high rate of fat deposition associated with hyperinsulinemia and glucose intolerance. We tested here the hypothesis that refeeding on a high-fat diet rich in essential polyunsaturated fatty acids (ePUFA) improves glucose homeostasis primarily by enhancing insulin sensitivity in skeletal muscles and adipose tissues. METHODS: Rats were caloric restricted for 2 weeks followed by 1-2 weeks of isocaloric refeeding on either a low-fat (LF) diet, a high-fat (HF) diet based on animal fat and high in saturated and monounsaturated fatty acids (HF SMFA diet), or a HF diet based on vegetable oils (1:1 mixture of safflower and linseed oils) and rich in the essential fatty acids linoleic and α-linolenic acids (HF ePUFA diet). In addition to measuring body composition and a test of glucose tolerance, insulin sensitivity was assessed during hyperinsulinemic-euglycemic clamps at the whole-body level and in individual skeletal muscles and adipose tissue depots. RESULTS: Compared to animals refed the LF diet, those refed the HF-SMFA diet showed a higher rate of fat deposition, higher plasma insulin and glucose responses during the test of glucose tolerance, and markedly lower insulin-stimulated glucose utilization at the whole body level (by a-third to a-half) and in adipose tissue depots (by 2-5 folds) during insulin clamps. While refeeding on the ePUFA diet prevented the increases in fat mass and in plasma insulin and glucose, the results of insulin clamps revealed that insulin-stimulated glucose utilization was not increased in skeletal muscles and only marginally higher in adipose tissues and at the whole-body level. CONCLUSIONS: These results suggest only a minor role for enhanced insulin sensitivity in the mechanisms by which diets high in ePUFA improves glucose homeostasis during catch-up growth.

Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization.

Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy. Our data indicated that mitochondria quality control adapted differently to immobilization and remobilization in GA and TA muscles. Data showed i) a disruption of mitochondria dynamic that occurred earlier in the immobilized TA, ii) an overriding role of mitophagy that involved Parkin-dependent and/or independent processes during immobilization in the GA and during remobilization in the TA, and iii) increased mitochondria biogenesis during remobilization in both muscles. This strongly emphasized the need to consider several muscle groups to study the mechanisms involved in muscle atrophy and their ability to recover, in order to provide broad and/or specific clues for the development of strategies to maintain muscle mass and improve the health and quality of life of patients.

Total energy expenditure assessed by doubly labeled water technique and estimates of physical activity in Mauritian children: analysis by gender and ethnicity.

BACKGROUND/OBJECTIVES: In the tropical island of Mauritius, the rise in obesity has accelerated in the past decades, and could be contributed by low physical activity and increased sedentary behavior. The study objectives were to generate the first dataset of total energy expenditure (TEE), to estimate physical activity in Mauritian children, and to explore differences due to gender and ethnicity. SUBJECTS/METHODS: The doubly labeled water (DLW) technique was used to evaluate TEE over 14 days in 56 Mauritian school children (aged 7-11 years) belonging to the two main ethnic groups: Indian (South Asian descent) and Creole (African/Malagasy descent). Physical activity level (PAL) was calculated as the ratio of TEE and resting energy expenditure (using Schofield equations), and daily step counts were measured by accelerometry. Anthropometry and body composition were also assessed. RESULTS: TEE measured by DLW was lower in Mauritian children (by ~155 kcal/d) than that predicted using FAO/WHO/UNU equations for children of the same sex, age, and body size. Furthermore, TEE, as well as PAL and step counts, also differed according to gender (lower in girls than in boys) and to ethnicity (lower in Indians than in Creoles) even after adjusting for differences in body weight and body composition. CONCLUSION: These results in Mauritian children provide the first dataset of objectively measured TEE, from which physical activity is estimated as PAL, and complemented by step counts measurements. They suggest potential gender and ethnic differences in TEE and physical activity that need consideration in developing strategies to counter sedentary behavior and obesity.

Oligosaccharides Isolated from MGO™ Manuka Honey Inhibit the Adhesion of Pseudomonas aeruginosa, Escherichia Coli O157:H7 and Staphylococcus Aureus to Human HT-29 cells.

Historically, honey is known for its anti-bacterial and anti-fungal activities and its use for treatment of wound infections. Although this practice has been in place for millennia, little information exists regarding which manuka honey components contribute to the protective nature of this product. Given that sugar accounts for over 80% of honey and up to 25% of this sugar is composed of oligosaccharides, we have investigated the anti-infective activity of manuka honey oligosaccharides against a range of pathogens. Initially, oligosaccharides were extracted from a commercially-available New Zealand manuka honey-MGO™ Manuka Honey (Manuka Health New Zealand Ltd)-and characterized by High pH anion exchange chromatography coupled with pulsed amperiometric detection. The adhesion of specific pathogens to the human colonic adenocarcinoma cell line, HT-29, was then assessed in the presence and absence of these oligosaccharides. Manuka honey oligosaccharides significantly reduced the adhesion of Escherichia coli O157:H7 (by 40%), Staphylococcus aureus (by 30%), and Pseudomonas aeruginosa (by 52%) to HT-29 cells. This activity was then proven to be concentration dependent and independent of bacterial killing. This study identifies MGO™ Manuka Honey as a source of anti-infective oligosaccharides for applications in functional foods aimed at lowering the incidence of infectious diseases.

Low 24-hour core body temperature as a thrifty metabolic trait driving catch-up fat during weight regain after caloric restriction.

The recovery of body weight after substantial weight loss or growth retardation is often characterized by a disproportionately higher rate of fat mass vs. lean mass recovery, with this phenomenon of "preferential catch-up fat" being contributed by energy conservation (thrifty) metabolism. To test the hypothesis that a low core body temperature (Tc) constitutes a thrifty metabolic trait underlying the high metabolic efficiency driving catch-up fat, the Anipill system, with telemetry capsules implanted in the peritoneal cavity, was used for continuous monitoring of Tc for several weeks in a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis. In animals housed at 22°C, 24-h Tc was reduced in response to semistarvation (-0.77°C, P < 0.001) and remained significantly lower than in control animals during the catch-up fat phase of refeeding (-0.27°C on average, P < 0.001), the lower Tc during refeeding being more pronounced during the light phase than during the dark phase of the 24-h cycle (-0.30°C vs. -0.23°C, P < 0.01) and with no between-group differences in locomotor activity. A lower 24-h Tc in animals showing catch-up fat was also observed when the housing temperature was raised to 29°C (i.e., at thermoneutrality). The reduced energy cost of homeothermy in response to caloric restriction persists during weight recovery and constitutes a thrifty metabolic trait that contributes to the high metabolic efficiency that underlies the rapid restoration of the body's fat stores during weight regain, with implications for obesity relapse after therapeutic slimming and the pathophysiology of catch-up growth.

Reduced Skeletal Muscle Protein Turnover and Thyroid Hormone Metabolism in Adaptive Thermogenesis That Facilitates Body Fat Recovery During Weight Regain.

Objective: The recovery of body composition after weight loss is characterized by an accelerated rate of fat recovery (preferential catch-up fat) resulting partly from an adaptive suppression of thermogenesis. Although the skeletal muscle has been implicated as an effector site for such thrifty (energy conservation) metabolism driving catch-up fat, the underlying mechanisms remain to be elucidated. We test here the hypothesis that this thrifty metabolism driving catch-up fat could reside in a reduced rate of protein turnover (an energetically costly "futile" cycle) and in altered local thyroid hormone metabolism in skeletal muscle. Methods: Using a validated rat model of semistarvation-refeeding in which catch-up fat is driven solely by suppressed thermogenesis, we measured after 1 week of refeeding in refed and control animals the following: (i) in-vivo rates of protein synthesis in hindlimb skeletal muscles using the flooding dose technique of 13C-labeled valine incorporation in muscle protein, (ii) ex-vivo muscle assay of net formation of thyroid hormone tri-iodothyronine (T3) from precursor hormone thyroxine (T4), and (iii) protein expression of skeletal muscle deiodinases (type 1, 2, and 3). Results: We show that after 1 week of calorie-controlled refeeding, the fractional protein synthesis rate was lower in skeletal muscles of refed animals than in controls (by 30-35%, p < 0.01) despite no between-group differences in the rate of skeletal muscle growth or whole-body protein deposition-thereby underscoring concomitant reductions in both protein synthesis and protein degradation rates in skeletal muscles of refed animals compared to controls. These differences in skeletal muscle protein turnover during catch-up fat were found to be independent of muscle type and fiber composition, and were associated with a slower net formation of muscle T3 from precursor hormone T4, together with increases in muscle protein expression of deiodinases which convert T4 and T3 to inactive forms. Conclusions: These results suggest that diminished skeletal muscle protein turnover, together with altered local muscle metabolism of thyroid hormones leading to diminished intracellular T3 availability, are features of the thrifty metabolism that drives the rapid restoration of the fat reserves during weight regain after caloric restriction.

Issues in Continuous 24-h Core Body Temperature Monitoring in Humans Using an Ingestible Capsule Telemetric Sensor.

BACKGROUND: There is increasing interest in the use of pill-sized ingestible capsule telemetric sensors for assessing core body temperature (Tc) as a potential indicator of variability in metabolic efficiency and thrifty metabolic traits. The aim of this study was to investigate the feasibility and accuracy of measuring Tc using the CorTemp® system. METHODS: Tc was measured over an average of 20 h in 27 human subjects, with measurements of energy expenditure made in the overnight fasted state at rest, during standardized low-intensity physical activity and after a 600 kcal mixed meal. Validation of accuracy of the capsule sensors was made ex vivo against mercury and electronic thermometers across the physiological range (35-40°C) in morning and afternoon of 2 or 3 consecutive days. Comparisons between capsule sensors and thermometers were made using Bland-Altman analysis. Systematic bias, error, and temperature drift over time were assessed. RESULTS: The circadian Tc profile classically reported in free-living humans was confirmed. Significant increases in Tc (+0.2°C) were found in response to low-power cycling at 40-50 W (~3-4 METs), but no changes in Tc were detectable during low-level isometric leg press exercise (<2 METs) or during the peak postprandial thermogenesis induced by the 600 kcal meal. Issues of particular interest include fast "turbo" gut transit with expulsion time of <15 h after capsule ingestion in one out of every five subjects and sudden erratic readings in teletransmission of Tc. Furthermore, ex vivo validation revealed a substantial mean bias (exceeding ±0.5°C) between the Tc capsule readings and mercury or electronic thermometers in half of the capsules. When examined over 2 or 3 days, the initial bias (small or large) drifted in excess of ±0.5°C in one out of every four capsules. CONCLUSION: Since Tc is regulated within a very narrow range in the healthy homeotherm's body (within 1°C), physiological investigations of Tc require great accuracy and precision (better than 0.1°C). Although ingestible capsule methodology appears of great interest for non-invasively monitoring the transit gut temperature, new technology requires a reduction in the inherent error of measurement and elimination of temperature drift and warrants more interlaboratory investigation on the above factors.