Obesity is now commonly defined in adults as a BMI > 30 kg/m2. The prevalence of obesity in established market economies (Europe, USA, Canada, Australia, etc.) varies greatly, but a weighed estimate suggests an average prevalence in the order of 15–20 %. The prevalence in these countries generally shows increasing trends over time. Obesity is also relatively common in Latin America, but much less so in sub-Saharan Africa and Asia where the majority of the world population lives. Nevertheless obesity rates are increasing there as well and, more importantly, rates of diabetes are increasing even more quickly, particularly in Asian countries. The risks of type 2 diabetes mellitus in these countries tend to increase sharply at levels of BMI generally classified as acceptable in European and North American white people. There have been suggestions to adopt specific classifications of obesity in Asians (e.g. BMI 23 for overweight and 25 or 27 kg/m2 for obesity) and this will greatly affect the prevalence estimates of obesity worldwide (currently at about 250 million people). Particularly for health promotion purposes BMI may be replaced by a classification based on waist circumference, but also specific classifications for different ethnic groups may be necessary. The number of diabetics has been projected to increase from 135 million in 1995 to 300 million in 2025. Much of this increase will be seen in Asia. In summary, both obesity and type 2 diabetes are common consequences of changing lifestyles (increased sedentary lifestyles and increased energy density of diets). Both are potentially preventable through lifestyle modification on a population level, but this requires a coherent and multifaceted strategy. Such strategies are not developed or implemented. These developments point toward the great urgency to develop global and national plans for adequate prevention and management of obesity and type 2 diabetes mellitus.

Although the rapid increase in the prevalence of obesity in many countries suggests that environmental factors (mainly overeating and physical inactivity) play the most important role in the development of overweight, it is very likely that genetic factors also contribute. It appears that one major gene in combination with one or several minor genes constitute the genetic components behind excess accumulation of body fat in most obese individuals. However, monogenic obesity has been described in a few families due to changes in leptin, leptin receptor, prohormone convertase, pro-opiomelanocortin or melanocortin-4 receptor. None of the monogenic variants is of great importance for common human obesity; the latter genes are unknown so far. Results from genomic scans suggest that major obesity genes are located on chromosomes 2, 10, 11 and 20. Studies of candidate genes indicate that the minor obesity genes control important functions of adipose tissue, and that structural variance in these genes may alter adipose tissue function in a way that promotes obesity. Such genes are β2- and β3-adrenoceptors, hormone-sensitive lipase, tumour necrosis factor alpha, uncoupling protein-1, low-density lipoprotein receptor, and peroxisome proliferator activator receptor gamma-2. Some of these genes may promote obesity by gene–gene interactions (for example β3-adrenoceptors and uncoupling protein-1) or gene–environment interactions (for example β2-adrenoceptors and physical activity). Some are important for obesity only among women (for example β2- and β3-adrenoceptors, low-density lipoprotein receptor and tumour necrosis factor alpha). Few ‘non-adipose’ genes have so far shown a firm association to common human obesity, which could suggest that the important genes for the development of excess body fat also control adipose tissue function.

The prevalence of obesity is reaching epidemic proportions in many industrialized countries. There is growing evidence that, even if the trigger of this epidemic is found in changes in the environment, genes are interacting with the environment to cause weight gain. Studies of twins reared apart indicate that approximately two-thirds of the variability in BMI is attributed to genetic factors. From prospective studies in Pima Indians we can ascribe 12 % of the variability in BMI to metabolic rate, 5 % to fat oxidation, and another probable 10 % to the level of spontaneous physical activity. These data indicate that at least 40 % of the variability in BMI is related to genetic factors involved in the regulation of food intake and/or volitional activity. This indicates that the most likely successful therapy for obesity may target pathways of the regulation of food intake. Similarly, an environment favouring engagement in physical activity should be promoted.

Population-based research on diet, obesity and the metabolic syndrome is faced with accumulating evidence of biases that may profoundly affect results. One potential source of bias, which is often neglected in nutritional epidemiology, arises from self-selected study populations. Subjects who agree to participate in surveys may be at less risk of metabolic syndrome than those who refuse. Analogous to observations in adult populations, studies of schoolchildren have also yielded clear evidence of self-selection. Whether such selection patterns influence analytical results depends on how the biases relate to the dependent and independent variables being studied. Systematic dietary reporting error is another source of bias in studies of nutritional risk factors for disease. While obesity-related under-reporting bias is now well documented, less is known about whether specific foods and nutrients are disproportionately affected. However, two studies employing biomarkers for protein have suggested that obese subjects under-reported the proportion of energy from fat plus carbohydrate. This should alert epidemiologists to the possibility that a dual reporting bias may be present in studies of diet and disease: general under-reporting among obese subjects compounded by food-specific errors. In summary, biases due to self-selection and selective dietary under-reporting may produce consequences in epidemiological studies that are both unpredictable and complex. We conclude this review with recent findings involving dietary fat intake and regional adiposity in a population-based study of women. These preliminary results may have etiological relevance to the development of metabolic syndrome, but multiple biases of the type described previously may also be operating.

The role of high-fat diets in weight gain and obesity has been questioned because of inconsistent reports in the literature concerning the efficacy of ad libitum low-fat diets to reduce body weight. We conducted a meta-analysis of weight loss occurring on ad libitum low-fat diets in intervention trials, and analysed the relationship between initial body weight and weight loss. We selected controlled trials lasting more than 2 months comparing ad libitum low-fat diets with a control group consuming their habitual diet or a medium-fat diet ad libitum published from 1966 to 1998. Data were included from 16 trials with a duration of 2–12 months, involving 1728 individuals. No trials on obese subjects fulfilled the inclusion criteria. The weighted difference in weight loss between intervention and control groups was 2.55 kg (95 % CI, 1.5–3.5; P < 0.0001). Weight loss was positively and independently related to pre-treatment body weight (r = 0.52,P < 0.05) and to reduction in the percentage of energy as fat (0.37 kg / %, P < 0.005) in unweighted analysis. Extrapolated to a BMI of about 30 kg/m2 and assuming a 10 % reduction in dietary fat, the predicted weight loss would be 4.4 kg (95 % CI, 2.0 to -6.8 kg). Because weight loss was not the primary aim in 12 of the 16 studies, it is unlikely that voluntary energy restriction contributed to the weight loss. Although there is no evidence that a high intake of simple sugars contributes to passive overconsumption, carbohydrate foods with a low glycaemic index may be more satiating and exert more beneficial effects on insulin resistance and cardiovascular risk factors. Moreover, an increase in protein content up to 25 % of total energy may also contribute to reducing total energy intake. In conclusion, a low-fat diet, high in protein and fibre-rich carbohydrates, mainly from different vegetables, fruits and whole grains, is highly satiating for fewer calories than fatty foods. This diet composition provides good sources of vitamins, minerals, trace elements and fibre, and may have the most beneficial effect on blood lipids and blood-pressure levels. A reduction in dietary fat without restriction of total energy intake prevents weight gain in subjects of normal weight and produces a weight loss in overweight subjects, which is highly relevant for public health.

Gain in body weight over a number of years could be achieved through cumulative positive energy balances. These positive balances could come about through adjustments in the various components of energy expenditure or fuel utilization, together with shifts in food selection or eating patterns leading to adjustments in macronutrient intake. This means that many combinations of intake and expenditure could lead to a positive energy balance; these combinations can be called routes to body weight gain. However, these routes are difficult to trace by studying random samples of individuals. Previous investigations have found a clear association between high fat consumption and the occurrence of obesity, and although a high fat intake is a strong behavioural risk factor for weight gain, the relationship does not constitute a biological inevitability. Some normal-weight and lean individuals appear to eat a high-fat diet. To investigate reasons for this we have studied individuals initially defined by particular clusters of dietary characteristics related to fat and carbohydrate consumption. Habitual high-fat (HF) and low-fat (LF) consumers have been termed phenotypes. Various aspects of energy expenditure (physiological and behavioural) and energy intake were measured in these individuals with contrasting profiles. HF phenotypes had high intakes of fatty foods and an overall higher energy intake than LF. However, these groups of young adult males had similar BMIs and percentage body fat. The HF had a significantly higher resting metabolic rate (RMR) and a lower RQ, together with high plasma fasting leptin levels, and a higher sleeping heart rate. In HF individuals the physical activity level was somewhat lower and they had significantly more periods of sedentary behaviour than LF subjects. Although HF individuals appear to be more vulnerable to developing obesity, both phenotypes carry particular risk factors and protective factors for weight gain. The use of phenotypes has allowed the identification of different potential routes to weight gain. Different strategies are required to prevent age-related increase in body weight in these quite different individuals.

The clustering of cardiovascular risk factors such as abdominal obesity, hypertension, dyslipidaemia and glucose intolerance in the same persons has been called the metabolic or insulin-resistance syndrome. In 1998 WHO proposed a unifying definition for the syndrome and chose to call it the metabolic syndrome rather than the insulin-resistance syndrome. Although insulin resistance has been considered as a common denominator for the different components of the syndrome, there is still debate as to whether it is pathogenically involved in all of the different components of the syndrome. Clustering of the syndrome in families suggests a genetic component. It is plausible that so-called thrifty genes, which have ensured optimal storage of energy during periods of fasting, could contribute to the phenotype of the metabolic syndrome. Common variants in a number of candidate genes influencing fat and glucose metabolism can probably, together with environmental triggers, increase susceptibility to the syndrome. Among these, the genes for β3-adrenergic receptor, hormone-sensitive lipase, lipoprotein lipase, IRS-1, PC-1, skeletal muscle glycogen synthase, etc. appear to increase the risk of the metabolic syndrome. In addition, novel genes may be identified by genome-wide searches.

Central obesity is a powerful predictor for disease. By utilizing salivary cortisol measurements throughout the day, it has now been possible to show on a population basis that perceived stress-related cortisol secretion frequently is elevated in this condition. This is followed by insulin resistance, central accumulation of body fat, dyslipidaemia and hypertension (the metabolic syndrome). Socio-economic and psychosocial handicaps are probably central inducers of hyperactivity of the hypothalamic–pituitary adrenal (HPA) axis. Alcohol, smoking and traits of psychiatric disease are also involved. In a minor part of the population a dysregulated, depressed function of the HPA axis is present, associated with low secretion of sex steroid and growth hormones, and increased activity of the sympathetic nervous system. This condition is followed by consistent abnormalities indicating the metabolic syndrome. Such ‘burned-out’ function of the HPA axis has previously been seen in subjects exposed to environmental stress of long duration. The feedback control of the HPA axis by central glucocorticoid receptors (GR) seems inefficient, associated with a polymorphism in the 5′ end of the GR gene locus. Homozygotes constitute about 14 % of Swedish men (women to be examined). Such men have a poorly controlled cortisol secretion, abdominal obesity, insulin resistance and hypertension. Furthermore, polymorphisms have been identified in the regulatory domain of the GR gene that are associated with elevated cortisol secretion; polymorphisms in dopamine and leptin receptor genes are associated with sympathetic nervous system activity, with elevated and low blood pressure, respectively. These results suggest a complex neuroendocrine background to the metabolic syndrome, where the kinetics of the regulation of the HPA axis play a central role.

This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play essential roles in the maintenance of energy balance and glucose metabolism. The data discussed indicate that dietary PUFA function as fuel partitioners in that they direct glucose toward glycogen storage, and direct fatty acids away from triglyceride synthesis and assimilation and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to have the unique ability to enhance thermogenesis and thereby reduce the efficiency of body fat deposition. PUFA exert their effects on lipid metabolism and thermogenesis by up-regulating the transcription of the mitochondrial uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while simultaneously down-regulating the transcription of genes encoding proteins involved in lipid synthesis (e.g. fatty acid synthase). The potential transcriptional mechanism and the transcription factors affected by PUFA are discussed. Moreover, the data are interpreted in the context of the role that PUFA may play as dietary factors in the development of obesity and insulin resistance. Collectively the results of these studies suggest that the metabolic functions governed by PUFA should be considered as part of the criteria utilized in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the optimum dietary ratio for n-6 : n-3 fatty acids.

Obesity, especially visceral adiposity, is a major determinant of the development of type 2 diabetes. Both visceral adiposity and insulin resistance are strongly related to cardiovascular risk factors in diabetic and non-diabetic subjects. One of the areas where the correlation between visceral fat (upper body adiposity) and cardiovascular risk is most apparent is the prediabetic state. We have recently shown that only prediabetic subjects (those who later develop type 2 diabetes) who are insulin resistant and with upper body adiposity have increased triglycerides, decreased HDL cholesterol and high blood pressure.

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.

It has long been recognized that acute elevation of non-esterified fatty acids (NEFA) stimulates insulin secretion to a moderate extent both in vitro and in vivo. The effects of longer-term exposure to elevated fatty acids have, however, been investigated only recently. Our own studies in the rat have documented the time dependence of NEFA effects, with inhibition of glucose-induced insulin secretion being apparent after 6–24 h in vivo exposure to Intralipid or in vitro exposure to palmitate, oleate and octanoate. Evidence indicates that the inhibitory effects are coupled to fatty acid oxidation in B-cells, with ensuing reduction in glucose oxidation, in parallel with diminished activity of the pyruvate dehydrogenase enzyme. These findings were essentially confirmed in human pancreatic islets. In the db/db mouse, a model of type 2 diabetes with obesity, evidence was obtained for elevated NEFA playing a significant role in decreased glucose-induced insulin secretion. Evidence also indicates that elevated NEFA inhibit insulin biosynthesis and increase the proinsulin : insulin ratio of secretion. Results on experimentally induced elevations of NEFA in non-diabetic and diabetic humans are thus far inconclusive. Further studies are needed to ascertain the impact of elevated NEFA on insulin secretion in clinical settings.

Critical insights into the etiology of insulin resistance have been gained by the use of animal models where insulin action has been modulated by strictly controlled dietary interventions not possible in human studies. Overall, the literature has moved from a focus on macronutrient proportions to understanding the unique effects of individual subtypes of fats, carbohydrates and proteins. Substantial evidence has now accumulated for a major role of dietary fat subtypes in insulin action. Intake of saturated fats is strongly linked to development of obesity and insulin resistance, while that of polyunsaturated fats (PUFAs) is not. This is consistent with observations that saturated fats are poorly oxidized for energy and thus readily stored, are poorly mobilized by lipolytic stimuli, impair membrane function, and increase the expression of genes associated with adipocyte profileration (making their own home). PUFAs have contrasting effects in each instance. It is therefore not surprising that increased PUFA intake in animal models is associated with improved insulin action and reduced adiposity. Less information is available for carbohydrate subtypes. Early work clearly demonstrated that diets high in simple sugars (in particular fructose) led to insulin resistance. However, again attention has rightly shifted to the very interesting issue of subtypes of complex carbohydrates. While no differences in insulin action have yet been shown, differences in substrate flux suggest there could be long-term beneficial effects on the fat balance of diets enhanced in slowly digested/resistant starches. A new area of major interest is in protein subtypes. Recent results have shown that rats fed high-fat diets where the protein component was from casein or soy were insulin-resistant, but when the protein source was from cod they were not. These are exciting times in our growing understanding of dietary factors and insulin action. While it has been clear for some time that ‘oils ain't oils’, the same is now proving true for carbohydrates and proteins.

A high intake of fat may increase the risk of obesity. Obesity, especially abdominal obesity, is an important determinant of the risk of developing insulin resistance and non-insulin-dependent diabetes mellitus. It is suggested that a high proportion of fat in the diet is associated with impaired insulin sensitivity and an increased risk of developing diabetes, independent of obesity and body fat localization, and that this risk may be influenced by the type of fatty acids in the diet. Cross-sectional studies show significant relationships between the serum lipid fatty acid composition, which at least partly mirrors the quality of the fatty acids in the diet, and insulin sensitivity. Insulin resistance, and disorders characterized by insulin resistance, are associated with a specific fatty acid pattern of the serum lipids with increased proportions of palmitic (16 : 0) and palmitoleic acids (16 : 1 n-7) and reduced levels of linoleic acid (18 : 2 n-6). The metabolism of linoleic acid seems to be disturbed with increased proportions of dihomo-gamma linolenic acid (20 : 3 n-6) and a reduced activity of the Δ5 desaturase, while the activities of the Δ9 and Δ6 desaturases appear to be increased. The skeletal muscle is the main determinant of insulin sensitivity. Several studies have shown that the fatty acid composition of the phosholipids of the skeletal muscle cell membranes is closely related to insulin sensitivity. An increased saturation of the membrane fatty acids and a reduced activity of Δ5 desaturase have been associated with insulin resistance. There are several possible mechanisms which could explain this relationship. The fatty acid composition of the lipids in serum and muscle is influenced by diet, but also by the degree of physical activity, genetic disposition, and possibly fetal undernutrition. However, controlled dietary intervention studies in humans investigating the effects of different types of fatty acids on insulin sensitivity have so far been negative.

The metabolic syndrome represents a vicious cycle whereby insulin resistance leads to compensatory hyperinsulinaemia, which maintains normal plasma glucose but may exacerbate insulin resistance. Excess insulin secretion may eventually reduce β-cell function due to amyloid deposition, leading to raised blood glucose and further deterioration of β-cell function and insulin sensitivity via glucose toxicity. Reducing postprandial glucose and insulin responses may be a way to interrupt this process, but there is disagreement about the dietary approach to achieve this. Glucose and insulin responses are determined primarily by the amount of carbohydrate consumed and its rate of absorption. Slowly absorbed, low glycaemic-index (GI) foods are associated with increased HDL cholesterol and reduced risk of type 2 diabetes. There is some evidence that low-GI foods improve insulin sensitivity in humans, although studies using established techniques (glucose clamp or frequently sampled intravenous glucose tolerance test) have not been done. Low carbohydrate diets have been suggested to be beneficial in the treatment of the metabolic syndrome because of reduced postprandial insulin. However, they may increase fasting glucose and impair oral glucose tolerance — effects which define carbohydrate intolerance. The effects of low carbohydrate diets on insulin sensitivity depend on what is used to replace the dietary carbohydrate, and the nature of the subjects studied. Dietary carbohydrates may affect insulin action, at least in part, via alterations in plasma free fatty acids. In normal subjects a high-carbohydrate/low-GI breakfast meal reduced free fatty acids by reducing the undershoot of plasma glucose, whereas low-carbohydrate breakfasts increased postprandial free fatty acids. It is unknown if these effects occur in insulin-resistant or diabetic subjects. Thus further work needs to be done before a firm conclusion can be drawn as to the optimal amount and type of dietary carbohydrate for the treatment of the metabolic syndrome.

Any intervention which causes negative energy balance is guaranteed to be efficacious in producing weight loss, which will continue while there is negative energy balance or be maintained as long as the new energy balance is maintained. In clinical practice compliance is rarely 100 % so the efficiency of even the most efficacious treatment is usually low. However, recent evidence-based guidelines have recognized the clinical benefits of moderate (5–10 %) weight loss, which is achievable using a variety of interventions. Long-term studies of ‘weight loss’ are, in reality, combinations of weight loss (usually completed in 1–6 months) followed by variable weight maintenance, set in the context of progressive adult weight gain in an obesogenic environment. Few studies have adopted specific and separate strategies for weight loss and weight maintenance. Meta-analyses conducted by non-expert methodologists have failed to recognize these distinctions, and have criticized the available research without understanding the different needs of studies with weight change as the outcome variable, which require randomized controlled trials (RCT), and those with weight loss as the treatment, intended to improve metabolic or biomedical outcome measures. An RCT design is inapplicable to studies of biomedical end points (e.g. cardiac risk factors) when weight loss is the treatment. Because fixed weight loss cannot be prescribed there is always a range of weight changes in any study, and single-sample studies with regression analysis provide the best design. An RCT study design does not give useful information about clinical value as the control group is always ‘treated’ to some extent. Placebo- (or control)-subtracted differences are misleading because in an RCT all subjects recruited to active treatment, including non-responders, are continued on treatment for the full duration of the study. In routine clinical practice, treatments are changed in the light of early experience as a therapeutic trial to optimize the results for each individual, and audit is required to evaluate ‘long term weight loss’.

Prevention of hypertension, and control of blood pressure in patients with hypertension, are necessary for the reduction of cardiovascular morbidity and mortality. Lifestyle modifications are one of the most important tools for effective lowering of blood pressure. Most randomized controlled studies have shown that even a modest weight loss of 3–9 % is associated with a significant reduction in systolic and diastolic blood pressure of roughly 3 mm Hg in overweight people. Limitation of sodium chloride in food has historically been considered the critical change for reducing blood pressure. Changes in sodium intake do affect blood pressure in older persons and in patients with hypertension and diabetes, whereas its role in population blood pressure has proven controversial. Recent meta-analyses indicate that adequate intake of minerals, e.g. potassium and probably calcium, rather than restriction of sodium, should be the focus of dietary recommendations. Although epidemiological data point to a direct relation between the intake of saturated fat, starch and alcohol, as well as an inverse relationship to the intake of omega-3 fatty acids and protein, our knowledge about macronutrients and blood pressure is scanty. It may well prove more productive to look at food instead of placing emphasis on single nutrients. Thus the Dietary Approaches to Stop Hypertension (DASH) demonstrates that a diet rich in fruits, vegetables, low-fat dairy products, fibre and minerals (calcium, potassium and magnesium) produces a potent antihypertensive effect. Such a diet is not very restrictive and should not produce compliance problems. Further high-quality research on the influence of macronutrients and food will yield data for updated recommendations, enabling better prevention and control of the blood pressure problem.

The increased risk of coronary heart disease associated with the metabolic syndrome may be partially explained by prothrombotic deviations of the haemostatic system. Individuals with insulin resistance, dyslipidaemia and obesity are characterized by elevated plasma fibrinogen and factor VII coagulant activity levels and raised concentrations of plasminogen-activator inhibitor, the main inhibitor of endogenous fibrinolysis. These haemostatic abnormalities may be corrected with dietary treatment of the underlying clinical disorder. Dietary trials of diseased and healthy volunteers suggest that the optimal antithrombotic diet is a low-fat diet with a high content of foods rich in complex carbohydrates and dietary fibre. The dietary fatty acid composition has a profound effect on blood lipids, but seems of minor importance for the haemostatic system.

Polymorphisms at the APOA1/C3/A4 gene cluster and the APOE gene have been extensively studied in order to examine their potential association with plasma lipid levels, coronary heart disease risk and more recently with inter-individual variability in response to dietary therapies. Although the results have not been uniform across studies, the current research supports the concept that variation at these genes explains a significant, but still rather small, proportion of the variability in fasting and postprandial plasma lipid responses to dietary interventions. This information constitutes the initial frame to develop panels of genetic markers that could be used to predict individual responsiveness to dietary therapy for the prevention of coronary heart disease. Future progress in this complex area will come from experiments carried out using animal models, and from carefully controlled dietary protocols in humans that should include the assessment of several other candidate gene loci coding for products that play a relevant role in lipoprotein metabolism (i.e. APOB, CETP, LPL, FABP2, SRBI, ABC1 and CYP7).