Obesity and metabolic disease: is adipose tissue the culprit?

Obesity is a risk factor for the development of type 2 diabetes and CVD. Is adipose tissue the culprit in the relationship between obesity and metabolic disease? It is certainly possible to argue that adipose tissue function is disturbed in obesity in such a way that adverse consequences may follow. For instance, lipolysis is down regulated, the sensitivity of lipolysis to insulin is reduced and there are disturbances in the regulation of adipose tissue blood flow. However, when examined critically these changes can be seen as adaptations to the increased adipose tissue mass, making the situation better rather than worse. In terms of the many peptide and other factors now known to be secreted from adipose tissue, it is easier to argue that adipose tissue is the culprit. However, for no single 'adipokine' is there as yet unequivocal evidence of a link between adipose tissue secretion and adverse metabolic events in other tissues. The best documented of these adipokines in relation to insulin resistance is adiponectin. Here, unusually, adiponectin confers insulin sensitivity, and its secretion is down regulated in obesity. It could be again that adipose tissue has down regulated its function in an attempt to compensate for its increased mass, although certainly that down-regulation is too extreme. On balance, it is clear that adipose tissue is a link in the chain of events leading to metabolic disease, but in many respects it is an innocent intermediary trying to deal with the consequences of positive energy balance, the real culprit.     

Brown adipose tissue: is it affected by intermittent hypoxia?

Background  

Intermittent hypoxia (IH), a model of sleep apnea, produces weight loss in animals. We hypothesized that changes in brown adipose tissue (BAT) function are involved in such phenomenon. We investigated the effect of IH, during 35 days, on body weight, brown adipose tissue wet weight (BATww) and total protein concentration (TPC) of BAT.     

A genetic future for coronary heart disease?

This paper is concerned with changing conceptions of genetic disease. It is based on an analysis of biomedical literature and focuses on the treatment of coronary heart disease (CHD) in four published commentary papers. The aim of this analysis is to explore the ways in which CHD is constructed as genetic and the place of genetic discourses in the wider set of ideas that circulate about the disease. This analysis is then used to consider some of the claims of the geneticisation thesis ( Lippman 1991 , 1992 ). The analysis suggests that a genetic vision for understanding and managing CHD has emerged, which has many of the hallmarks of the geneticisation imagined by Lippman. However, a number of alternative and competing models of CHD are also supported within the biomedical discourse. These are related to the different disciplines with a stake in the field of CHD, and their struggles for authority. In conclusion, it is suggested that the geneticisation thesis, as a universal claim, is at odds with the diffuse and distributed nature of biomedical knowledge and practice. Rather than analysing geneticisation in a literal way, it may be more fruitful to see the thesis, itself, as a form of boundary work ( Gieryn 1983 ).     

Do calorie restriction or alternate-day fasting regimens modulate adipose tissue physiology in a way that reduces chronic disease risk?

Adipose tissue physiology plays an important role in the development of several obesity-related disorders. Dietary restriction regimens, i.e., daily calorie restriction (CR) or alternate-day fasting (ADF), have been shown to decrease the risk of these disorders. Whether changes in adipose mass or physiology are required for the beneficial effects of CR or ADF is an important question. Accordingly, this review summarizes the effects of CR and ADF regimens on parameters of adipose physiology, i.e., adipose tissue morphology, triglyceride metabolism, and adipokine release, and attempts to link these changes to indicators of chronic disease risk.     

A prospective study of organochlorines in adipose tissue and risk of non‑Hodgkin lymphoma

Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements.Objective: Our purpose was to examine associations between organochlorine concentrations in prediagnostic adipose tissue samples and the risk of NHL.Methods: We conducted a case–cohort study using a prospective Danish cohort of 57,053 persons enrolled between 1993 and 1997. Within the cohort we identified 256 persons diagnosed with NHL in the population-based nationwide Danish Cancer Registry and randomly selected 256 subcohort persons. We measured concentrations of 8 pesticides and 10 polychlorinated biphenyl (PCB) congeners in adipose tissue collected upon enrollment. Associations between the 18 organochlorines and NHL were analyzed in Cox regression models, adjusting for body mass index.Results: Incidence rate ratios and confidence intervals (CIs) for interquartile range increases in concentrations of dichlorodiphenyltrichlorethane (DDT), cis-nonachlor, and oxychlordane were 1.35 (95% CI: 1.10, 1.66), 1.13 (95% CI: 0.94, 1.36), and 1.11 (95% CI: 0.89, 1.38), respectively, with monotonic dose–response trends for DDT and cis-nonachlor based on categorical models. The relative risk estimates were higher for men than for women. In contrast, no clear association was found between NHL and PCBs.Conclusion: We found a higher risk of NHL in association with higher adipose tissue levels of DDT, cis-nonachlor, and oxychlordane, but no association with PCBs. This is the first study of organochlorines and NHL using prediagnostic adipose tissue samples in the exposure assessment and provides new environmental health evidence that these organochlorines contribute to NHL risk.     

'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?

Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.     

The development of β1-adrenoreceptors in brown adipose tissue following prenatal alcohol exposure

Prenatal alcohol exposure delays the development of thermoregulation in newborn rats. Newborns generate heat by the sympathetic nervous system's activation of nonshivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of prenatal alcohol exposure on the development of the β-adrenergic receptor system of BAT was investigated by assessing the number and pharmacological properties of β-adrenergic receptors in BAT in 1-, 5-, 10-, and 20-day-old offspring. Pregnant dams were given either a liquid diet with 35% of the calories derived from alcohol, a liquid diet without alcohol to control for any effects of the liquid diet administration, or ad lib food and water. Offspring from the alcohol prenatal treatment group had a greater number of β₁ adrenergic receptors compared to offspring from both from the pair-fed and lab chow control groups, which did not differ from each other. The greater number of receptor sites in 5-day-old subjects suggests that the number of binding sites in alcohol-exposed BAT cells continues to rise due to the absence of sufficient neurotransmitter, and perhaps reflects a delay in the arrival of sympathetic nervous system neurons. During the second and third postnatal weeks, when NE concentrations are rising and reaching asymptotic levels, the number of β₁ adrenergic receptors in BAT of control subjects is decreasing. This expected compensatory “downregulation” response in receptor concentration was not seen in BAT from subjects exposed to alcohol prenatally. These findings may have important implications for understanding the effects of prenatal alcohol exposure on developing plasticity in the peripheral nervous system.     

An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development?

A positive energy balance (energy intake>energy expenditure), in which total fat intake plays an important role, is commonly regarded as a major factor contributing to obesity. Adipose tissue development, i.e. both size (hypertrophy) and number (hyperplasia), is stimulated by high dietary fat intake during early postnatal development, a susceptibility that now appears to continue well into adulthood. Recent human and animal studies suggest that by altering rates of adipocyte differentiation and proliferation, differences in the composition of dietary fat may also contribute to adipose tissue development. At least in rodent models, the relative intake of n-6 to n-3 PUFA is clearly emerging as a new factor in this development. In these models, higher linoleate intake raises tissue arachidonic acid, which increases prostacyclin production and, in turn, stimulates signalling pathways implicated in adipogenesis. Signalling pathways stimulated by arachidonic acid probably include phospholipase and/or cyclo-oxygenase activation and may be linked as much to relatively low intake of n-3 PUFA as to excessive dietary linoleate. One factor potentially contributing to oversight about the apparent role of dietary n-6 PUFA (especially excess dietary linoleate) in adipose tissue development is the historical overestimation of linoleate requirements and the enthusiasm for higher intake of 'essential fatty acids'. More research is needed to address whether disequilibration of dietary PUFA intake contributes to the risk of obesity in humans.     

Effects of physical activity on adipose tissue cellularity in premenopausal obese women in Bénin

The purpose of this article was to quantify the exercise load and investigate the influence of physical exercise on adipose tissue in obese women from Bénin. Twelve subjects participated at the study. Six of the subjects trained three times a week for six months. Each training session lasted forty-five minutes. The remaining six women constituted the control group. Biopsy samples of adipose tissue were taken from the same site in the gluteal iliac region at the end of six months and analyzed by histochemistry and electron microscopy. The results showed that all subjects suffered from severe central obesity; lipid content and number of adipocytes were higher among the sedentary woman than among those who exercised. Intense exercise in the latter used more lipids than carbohydrates. We conclude that regular, supervised physical exercise reduces lipid levels and thus induces weight loss.     

A 24-hour fast-induced loss of energetic substrates in the interscapular brown adipose tissue of ‘cafeteria’ rats

The incorporation of tracer-labelled glucose and alanine, as well as the levels of energetic components in interscapular brown adipose tissue of male rats fed either standard or ‘cafeteria’ diet have been studied in fed and 24-hour of food withdrawal situations. The relative amount of brown adipose tissue in cafeteria fed rats was much greater than in controls, whose size and composition were not altered with food withdrawal. Cafeteria fed rats lost significant amounts of both lipid and protein during food withdrawal. Label incorporation was comparable for glucose and alanine except within the lipidic fraction, in which cafeteria fed rats showed a considerably lower efficiency. The loss of protein with food withdrawal and the swift incorporation of alanine into protein, tissue amino acid pools and lipids suggest an easy utilization of these amino acids by both groups of rats. In addition, the loss of energetic substrates observed in the cafeteria fed rats during food withdrawal suggests a continued utilization of energetic substrates by this brown adipose tissue, a condition not observed in the tighter energetic budget of control rats.     

Breast implants: is there an association with connective tissue disease?

Following concern over a suggested link between the implantation of silicone gel and connective tissue disease, the Medical Devices Directorate (MDD) of the Department of Health reviewed all available data for submission to a specially convened Expert Advisory Group. Animal studies indicated that silicones are unlikely to stimulate a specific antibody response or cell-mediated immunity, that they have no adverse effect on resistance to infection, and produce minimal effects in the presence of potent adjuvants but can act as adjuvants themselves. The connective tissue disease most commonly claimed to be associated with breast implants is scleroderma. Although one series of patients showed a significantly higher prevalence of this disease than expected, there is no clear indication that the incidence of scleroderma in women with breast implants is any higher than in the general population.     

β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

Background

Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet.

Methods

Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study.

Results

In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet.

Conclusions

These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.     

Does periodontal disease cause cardiovascular disease? Analysis of epidemiological evidences

This article reports a critical analysis of epidemiologic studies that evaluated periodontal disease as a cause of cardiovascular disease. Thirty-five studies were identified through a manual search of the special abstracts volumes of the Journal of Dental Research, as well as an electronic search on MEDLINE, LILACS, and ISI and inspection of the articles' bibliographies. Inclusion criteria were: articles in any language published between 1989 and 2000 reporting the presence or absence of an association between periodontal and cardiovascular diseases. Available studies are scarce, and interpretations are limited by potential bias and confounding. The studies analyzed (whether separately or jointly) fail to provide convincing epidemiologic evidence for a causal association between periodontal and cardiovascular diseases. Although the possibility that oral diseases can cause cardiovascular diseases cannot be discarded, until better data are available, periodontal disease should not be incriminated as a cause of cardiovascular disease.