Michel Lacaille

Genome-wide search for genes related to the fat-free body mass in the Québec family study

Fat-free mass (FFM) consists mostly of skeletal muscle and bone tissues, and identification of the genes and molecular mechanisms involved in the control of FFM would have implications for the understanding of sarcopenia and potentially osteoporesis associated with aging, as well as the response to starvation, refeeding, anorexia, and any other conditions in which lean body mass is important. A genome-wide search for genes related to body leanness has been completed in the Quebec Family Study (QFS). Microsatellite markers (N = 292) from the 22 autosomal chromosomes were typed. The mean spacing of the markers was 11.9 centimorgans (cM) (range, <0.1 to 41). FFM was calculated from percent body fat, derived from underwater weighing, and body weight and was adjusted by regression for age and sex effects before analysis. A maximum of 336 sib pairs or 609 pairs of extended relatives were analyzed using single-point Haseman-Elston regression (SIBPAL and RELPAL) and multipoint variance component (SEGPATH) linkage analyses. Significant linkages were observed on chromosomes 15q25-q26 for a CA repeat within the insulin-like growth factor 1 receptor (IGF1R) gene (Lod score = 3.56) and at 18q12 with D18S877 (Lod score = 3.53) and D18S535 (Lod score = 3.58), 2 markers located 10 cM apart. A moderately significant linkage was also observed on chromosome 7p15.3 with the marker D7S1808 (Lod score = 2.72). The most obvious candidate genes within the regions identified by these linkages include the IGF1R on 15q and neuropeptide Y (NPY) and growth hormone-releasing hormone (GHRH) receptor on 7p. On 18q, the melanocortin receptor 4 (MC4R) is not likely the candidate gene for the observed linkage. This study represents the first genome-wide search for genes that may be involved in the regulation of the lean component of body mass in humans.

Enzymatic adaptations to suspension hypokinesia in skeletal muscle of young and old rats

Hindlimb hypokinesia was induced in young and old rats. After 3 weeks, the activities of five enzymes have been measured in soleus and medial gastrocnemius muscles. Soleus showed increased activity of hexokinase and decreased activity of phosphofructokinase, lactate dehydrogenase and malate dehydrogenase in both groups. The activity of 3-hydroxyacyl-CoA-dehydrogenase was decreased in the old muscle. Medial gastrocnemius showed decreased activity of phosphofructokinase and lactate dehydrogenase in both groups. The activity of 3-hydroxyacyl-CoA-dehydrogenase was decreased in the old muscle whereas hexokinase increased its activity in the young one. It is concluded that suspension hypokinesia results in changes at the enzymatic level. These changes appear to be related to the age of the muscle and to its fibre composition.

Effects of hypokinesia/hypodynamia on contractile and histochemical properties of young and old rat soleus muscle

To determine if the atrophic process was different in the young and in the aged slow-twitch soleus muscle, in which the aging process is clearly apparent, hind limb hypokinesia/hypodynamia was induced. After 3 weeks, we measured speed-related indices, tension indices, and tension producing capacities. Fiber type composition and fiber cross-sectional area were also investigated. After the treatment, body weight and muscle weight decreased, the most important loss being measured in the young group. The ratio of muscle weight to body weight was not altered by hypokinesia/hypodynamia but this ratio was greater in the 3-month-old control group than in the 22-month-old group. Contraction time and half-relaxation time decreased in both groups. In the control group, the old soleus muscle was slower to contract and relax than in the young muscle. Tension indices and tension producing capacities decreased. These included twitch tension, maximally developed tension, force generated per gram muscle, and specific tension. The mean muscle area and muscle weight of the young soleus decreased more than that of the old soleus. The fiber cross-sectional area was reduced in both groups whereas fiber type composition remained the same after hypokinesia/hypodynamia. The suspension atrophy appeared to be independent of age in the soleus at the contractile level whereas atrophy was greater in the young muscle at the morphometric level.

Contractile and histochemical properties of young and old medial gastrocnemius muscle after suspension hypokinesia/hypodynamia

In order to determine if the atrophic process was different in the young and in the aged fast twitch medial gastrocnemius muscle, in which the aging process is clearly apparent, hindlimb hypokinesia/hypodynamia (H/H) was induced on rats. After 3 weeks, we measured speed-related indices, tension indices and tension producing capacities. Fiber type composition and fiber cross-sectional area were also determined. The body weight and muscle weight decreased. The ratio of muscle weight to body weight was greater in the 3-month-old control group than in the 22-month-old group. However, the ratio was not altered by H/H. In both groups, contraction time, half relaxation time and twitch tension did not vary with H/H but maximally developed tension and force generated per gram of muscle were decreased. For the histochemical analysis, the medial gastrocnemius muscle was divided in its red and white parts. Fiber type composition remained the same after H/H in both parts of the muscle and in both groups of age except for an increase of the FOG fiber type proportion in the red part of the old group. Fiber cross-sectional area increased with age and decreased after the suspension except for the fast fibers in the white part of the aged muscle. The most affected group in fiber cross-sectional (SO-FOG-FG) area after suspension was the white part of medial gastrocnemius in the young group. The suspension atrophy appeared to be independent of age in the medial gastrocnemius at the contractile level whereas atrophy was greater at the histochemical level in the young muscle. With age, fiber cross-sectional area increased particularly in the red part of the muscle.

Impact of Walking on Adipose Tissue Lipoprotein Lipase Activity and Expression in Pre- and Postmenopausal Women

Objective: The aim of this study was to examine regional variation in adipose tissue lipoprotein lipase (AT-LPL) activity and expression in pre-and postmenopausal women, before and after training, once differences in chronological age or obesity degree are taken into account. Methods: Sixteen late pre- and 14 early postmenopausal (49 ± 2 vs. 52 ± 2 years; p < 0.001) moderately obese women (body mass index 29–35 kg/m2) were subjected to a 16-week walking program (3 sessions/week of 45 min at 60% heart rate reserve). Abdominal and femoral AT-LPL activity and expression, fasting lipidlipoprotein profile, body composition, and cardiorespiratory fitness (CRF) were measured before and after our intervention. Statistical analyses were performed using covariance analysis for age differences. Results: AT-LPL activity and expression, lipid-lipoprotein metabolism, body fatness, and CRF were similar at baseline, irrespective of the group considered. Slight reductions in plasma cholesterol and high-density lipoprotein (HDL) cholesterol levels, fat mass and waist girth reductions, CRF increases as well as femoral AT-LPL activity and expression decreases after our intervention were comparable, regardless of menopausal status (0.0001 < p < 0.05). Conclusions: Lipid storage is decreased in the femoral depot after walking, regardless of menopausal status. Reduction in AT-LPL activity or expression does not lead to a more deleterious lipid-lipoprotein profile, despite the modest decrease noted in HDL cholesterol concentrations.

Enzymatic activities in slow and fast denervated old rat muscles

The activities of five enzymes have been studied quantitatively in denervated extensor digitorum longus, gastrocnemius and soleus muscles of 24-month-old rats. The results have been compared with those obtained from normal muscles of a similar age group of rats. Three weeks after denervation, the activity of hexokinase was increased in gastrocnemius and extensor digitorum longus. Phosphofructokinase, lactate dehydrogenase, malate dehydrogenase and 3-hydroxyacyl-CoA-dehydrogenase showed decreased activities. These results suggest that enzyme which represents glucose uptake increased its activity in fast muscles and that enzymes for anaerobic glycolysis, lactate fermentation, citric acid cycle and beta-oxidation had a decreased activity in slow and fast muscles.

Effects of electrical stimulation on the activity of hexokinase in the medial gastrocnemius muscle of aged rats after hindlimb suspension

1. The activity of the enzyme Hexokinase (E.C. 2.7.1.1.) has been measured after a 21 day period of hindlimb suspension and a 14 day period of recovery with or without electrical stimulation in the old rat Medial Gastrocnemius muscle divided in its white and red parts. 2. After suspension, the activity of the enzyme increased in both parts of the muscle and returned near its control value more rapidly in the red part of the muscle when electrical stimulation was applied.

High ApoD protein level in the round ligament fat depot of severely obese women is associated with an improved inflammatory profile

PurposeApolipoprotein D (ApoD) is a lipocalin participating in lipid transport. It binds to a variety of ligands, with a higher affinity for arachidonic acid, and is thought to have a diverse array of functions. We investigated a potential role for ApoD in insulin sensitivity, inflammation, and thrombosis—processes related to lipid metabolism—in severely obese women.MethodsWe measured ApoD expression in a cohort of 44 severely obese women including dysmetabolic and non-dysmetabolic patients. Physical and metabolic characteristics of these women were determined from anthropometric measurements and blood samples. ApoD was quantified at the mRNA and protein levels in samples from three intra-abdominal adipose tissues (AT): omental, mesenteric and round ligament (RL).ResultsApoD protein levels were highly variable between AT of the same individual. High ApoD protein levels, particularly in the RL depot, were linked to lower plasma insulin levels (−40%, p = 0.015) and insulin resistance (−47%, p = 0.022), and increased insulin sensitivity (+10%, p = 0.008). Lower circulating pro-inflammatory PAI-1 (−39%, p = 0.001), and TNF-α (−19%, p = 0.030) levels were also correlated to high ApoD protein in the RL AT.ConclusionsApoD variability between AT was consistent with different accumulation efficiencies and/or metabolic functions according to the anatomic location of fat depots. Most statistically significant correlations implicated ApoD protein levels, in agreement with protein accumulation in target tissues. These correlations associated higher ApoD levels in fat depots with improved metabolic health in severely obese women.