. Ukkola O, Tremblay A, Bouchard C (Louisiana State University, Baton Rouge, LA, USA; University of Oulu, Oulu, Finland; and Laval University, Ste‐Foy, Quebec, Canada). Lipoprotein lipase polymorphisms and responses to long‐term overfeeding. J Intern Med 2002; 251: 429–436. Objectives. The role of the lipoprotein lipase (LPL) gene Hind III, S447X, Bam HI and Pvu II polymorphisms on body composition and lipid and lipoprotein changes in response to long‐term overfeeding was studied. Subjects. Twelve pairs of male monozygotic twins ate a 4.2 MJ day −1 energy surplus, 6 days a week, during a period of 100 days. Results. Overfeeding induced a decrease in high‐density lipoprotein 2 cholesterol (HDL 2 ‐C) and HDL 2 ‐C to HDL 3 ‐C ratio in the H2H2 ( n = 12) subjects of the LPL Hind III polymorphism. In contrast, the H1H1/H1H2 ( n = 12) subjects experienced increases both in the HDL 2 ‐C and HDL 2 ‐C to HDL 3 ‐C ratio ( P = 0.009 and 0.007, respectively, for differences in percentage changes between H2H2 and H1H1/H1H2). In addition, the H2H2 genotype was associated with higher levels of very‐low‐density lipoprotein triglyceride (VLDL‐TG) ( P < 0.03) and VLDL‐C ( P < 0.05) before and after overfeeding and higher HDL‐TG levels ( P < 0.003) after overfeeding. Postheparin lipoprotein lipase (PH‐LPL) activity tended to increase in H1H1/H1H2 and decrease in H2H2 subjects. The H2H2 subjects had lower total HDL‐C than those with the genotype H1H1/H1H2 4 months and 5 years after overfeeding ( P = 0.04 and 0.10, respectively). The plasma lipid differences were similar amongst subjects with the S447S ( n = 4) genotype of the S447X and H2H2 genotype of the Hind III polymorphisms. Body composition changes in response to overfeeding were not different between the Hind III genotypes. LPL Pvu II and Hind III polymorphisms were associated weakly with body weight gain ( P = 0.015–0.039) but strongly with adipose tissue LPL activity ( P < 0.01) after the caloric surplus. Conclusions. We conclude that the H2H2 subjects of the LPL gene Hind III polymorphism experience a decrease in the concentration of antiaterogenic lipoproteins when they are exposed to long‐term positive energy balance. This may have been partly caused by a diminished catabolism of TG‐rich particles in H2H2 subjects. LPL Pvu II and Bam HI polymorphisms were associated with body weight gain and adipose tissue LPL activity. Genetic variation at the LPL locus could thus be one of the factors responsible for the inter‐individual differences observed in plasma lipid and lipoprotein responses to chronic positive energy balance. It must be kept in mind that the sample size for this study was small. Nonetheless, it provides useful information on the genes and pathways that should be further explored.
It is still not possible to provide an evidence-based answer to the question of whether regular exercise is essential for normal growth. It is also unclear whether very low levels of exercise result in growth deficits. Regular exposure to exercise is characterized by heterogeneity in responsiveness, with most individuals experiencing improvements in fitness traits but a significant proportion showing only very minor gains. Whether a sedentary mode of life during the growing years results in a permanent deficit in cardiorespiratory fitness or a diminished ability to respond favorably to regular exercise later in life remains to be investigated. Although several genes have been associated with fitness levels or response to regular exercise, the quality of the evidence is weak mainly because studies are statistically underpowered. The special case of the obese, sedentary child is discussed, and the importance of the "energy gap" in the excess weight gain during growth is highlighted. Obese, sedentary children have high blood pressure, dyslipidemia, elevated glycemia and type 2 diabetes, hepatic steatosis, respiratory problems, orthopedic complications, and other health disorders more frequently than normal weight, physically active children. The role of genetic differences in the inclination to be sedentary or physically active is reviewed. An understanding of the true role of genetic differences and regular exercise on the growth of children will require more elaborate paradigms incorporating not only DNA sequence variants and exercise exposure but also information on nutrition, programming, and epigenetic events during fetal life and early postnatal years.
From a total of 12 pairs of young male identical twins who were overfed by an estimated 84,000 kcal over a period of 100 days, several pairs (eight to 11, depending on variables) were remeasured for body weight, body composition with the underwater weighing technique, regional fat distribution from skinfolds, girths, computed tomography (CT) fat areas in the abdominal region, and fasting plasma glucose, insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides 4 months and 5 years after completion of the overfeeding protocol. At 4 months, the twins had lost approximately 7 of 8 kg that they had gained with overfeeding. However, 5 years later, body weight had increased by 5 kg over the preoverfeeding level. Fluctuations in fat mass were greater than those in fat-free mass. The younger twins gained approximately twice as much as the older twins in the late recovery period, a difference attributed to the late phase of growth in body mass in the former. Upper-body fat was reduced at 4 months of follow-up study, but was increased in the late recovery phase. All blood values were normalized in the postoverfeeding periods. A within-pair resemblance was generally observed for the changes noted in the recovery periods, but it was more striking when variations between preoverfeeding and 4-month or 5-year values were considered. We conclude from these observations that there were no persistent effects of exposure to the overfeeding protocol over the expected age-associated increases in body mass, body fat, upper-body fat, abdominal visceral fat (AVF), and metabolic variables predictive of risk for common diseases in individuals of normal body weight and with no family history of obesity. The intrapair resemblance suggests that the genotype contributes to the alterations observed in the recovery from overfeeding and in the age-associated changes.
No abstract is provided for this article.
Obesity is a highly prevalent chronic disease that carries enormous human and economical costs in Western nations. The early chapters of the book revealed that the prevalence of overweight and obesity was already quite high in Western societies and on the rise in developing countries of the world. The investigation of the association between DNA sequence variation at specific genes and obesity phenotypes has just begun. The limited molecular marker studies published so far suggest that there will likely be several genes associated and/or linked with human obesity. Recent progress in animal genetics, transfection systems, transgenic animal models, recombinant DNA technologies applied to positional cloning, and methods to identify loci contributing to quantitative traits have provided a new impetus to this field. An important contemporary issue is whether there are genotype-environment effects and/or gene-gene effects which influence the events leading to the various obesity phenotypes or to some of their outcomes.
▪ Abstract This review summarizes the research advances of the past decade regarding the role of human genetic differences in energy and nutrient intake as well as in eating behavior phenotypes and selected eating disorders. The evidence for familial aggregation and heritability based on twin and nuclear family study designs is summarized. Genome-wide linkage scans and quantitative trait loci identified to date are discussed. DNA sequence variants in candidate genes are reviewed. Single genes associated with classical eating disorders are also incorporated. Epigenetic events will need to be incorporated in future studies designed to investigate the effects of DNA variants on dietary phenotypes. Understanding the relative contribution of global genetic variation and of DNA sequence variants in specific genes is important in the effort to influence dietary habits in a healthier direction.
