Current Nutrition & Food Science

ISSN: 1573-4013

Current Nutrition & Food Science
Volume 3, Number 2, May 2007

Contents

Dietary Determinants of the Metabolic Syndrome
Guest Editor: Luc Tappy
Co-Editors: Jacques Delarue and Kim-Anne Lê

Editorial Pp. 109-111


Epidemics of Obesity and Metabolic Disorders: Are Dietary Fats or Sugars Involved? Pp. 113-121
George A. Bray and Barry M. Popkin
[Abstract]


Pharmacological Treatment of Obesity, Food Intake, and Reversal of Metabolic Disorders Pp. 123-133
A.J. Scheen and N. Paquot
[Abstract]


Dietary Factors in Childhood Obesity Pp. 135-140
Patrick Tounian
[Abstract]


Non-Alcoholic Fatty Liver Disease in Children Pp. 141-144
Papandreou Dimitrios, Rousso Israel and Mavromichalis Ioannis
[Abstract]


Reversal of Diabetes and Metabolic Disorders After Bariatric Surgery Pp. 145-150
Melania Manco, Laura Leccesi and Geltrude Mingrone
[Abstract]


Can Marine Omega 3 Fatty Acids Prevent and/or Treat Metabolic Syndrome? Pp. 151-156
J. Delarue, V. Le Guen, G. Allain, C. Corporeau and S. Guillerm
[Abstract]


Physical Activity and Insulin Resistance Pp. 157-160
Guy Plasqui and Klaas R. Westerterp
[Abstract]


General Articles


Occurrence and Biological Properties of Sphingolipids – A Review Pp. 161-173
Karin Wehrmüller
[Abstract]


Olive Oil and Haemostasis Pp. 175-182
Javier Delgado-Lista, Jose Lopez-Miranda, Pablo Perez-Martinez, Juan Ruano, Francisco Fuentes and Francisco Perez-Jimenez
[Abstract]




Abstracts


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Editorial

Over the past decades, there has been a tremendous rise in the prevalence of obesity, not only in the westernized countries, but all over the world. Although it is well recognized that genetic factors are involved in obesity, this rapid rise is essentially to be attributed to environmental factors; indeed, the human gene pool is unlikely to have changed substantially over such a short period! However, this does not exclude that inside this gene pool some genes may be more expressed or repressed in response to environmental factors, which may in turn lead to metabolic disorders. In this regard, the observation that a Paleolithic diet confers, at least in domestic pigs, a higher insulin sensitivity, a lower blood pressure and a lower C reactive protein level (a surrogate marker of cardiovascular risk) as compared to a cereal-based diet may also be of some interest in an evolutionary perspective [1]. Changes in lifestyle, including increased urbanization, a shift from rural activities - with high energy expenditure - to sedentarity, office jobs and urban environments, increased reliance on motorized vehicles for transportation, increased daily time spent watching TV, and changes in diet, are amongst the numerous factors which can be incriminated in the present rise in obesity observed in Africa and South-eastern Asia. Although these changes in lifestyle occurred several decades earlier in the Westernized countries, present observations suggest that the same factors have been involved in the current epidemics of obesity in North America and in Europe [2].

Obesity is closely associated with several disorders, whose prevalence is also on the rise, including type 2 diabetes mellitus, high blood pressure, dyslipidemia (low HDL cholesterol, high triglycerides) and atherosclerotic heart disease [3,4]. Furthermore, all these conditions frequently occur as clusters in the same individual. Almost 20 years ago, G. Reaven presented evidences from his own work and from the literature that insulin resistance was often present in different distinct diseases, i.e., type 2 diabetes mellitus, dyslipidemia and high blood pressure. He further proposed the hypothesis that insulin resistance was the common factor at the origin of the development of all these conditions, which might explain their clustering [5].

This concept has arisen a lot of interest in both researchers and clinicians. Numerous epidemiological studies have indeed documented the clustering of insulin resistance, T2DM or glucose intolerance, dyslipidemia, high blood pressure and coronary heart disease. The condition, initially referred to as “syndrome X”, has since been renamed as “metabolic syndrome”. A medline search for this entity over the past 10 years yielded over 5000 hits, demonstrating the extent of its appeal to both researchers and clinicians. It is now well documented that this syndrome is highly prevalent in the Westernized countries, and is likely to increase rapidly in other countries as well. The concept, definition and practical use of the metabolic syndrome are not without controversy, however. First, several definitions and diagnostic criteria have been proposed by different associations (Table 1). For the U.S. National Cholesterol Education Program (NCEP/ATPIII) [6], abdominal obesity, dyslipidemia, high blood glucose and high blood pressure are used as exclusive criteria. Since all of these are by themselves risk factors for cardiovascular diseases, detecting their simultaneous occurrence in the same individual most likely identifies individuals at markedly increased risk for heart disease; in a simplistic way, one could say that it is the cardiologist’s definition of the syndrome. For the World Health organization (WHO) [7], diabetes or impaired glucose tolerance or insulin resistance is an obligatory criterion, with at least 2 of the other NCEP/ATPIII criteria; given the focus put on insulin resistance, individuals applicable to this definition may be particularly prone to develop diabetes mellitus; a diabetologist definition of the syndrome. Finally, the more recent International Diabetes Federation (IDF) consensus [8] puts the focus on abdominal/visceral obesity. In this regard, it is apparent from epidemiological data that normal values for waist circumference (which are used as a clinical proxy for visceral obesity) differ according to ethnic groups, a fact that was incorporated in the IDF criteria. Although there is a considerable overlap of the cases of metabolic syndrome using these different criteria in the same population, concordance is far from complete [9]. The clinical relevance of diagnosing the metabolic syndrome has also been recently challenged [10,11]. Although it is widely documented that individuals with the metabolic syndrome (whatever the criteria used) have a markedly increased risk for coronary heart disease, evidence is lacking that clustering of these factors leads to a greater risk than the sum of the risks associated with each individual factors. As a consequence, it is advocated to treat all individual risk factors irrespective of the diagnosis of the metabolic syndrome. From a pharmacotherapeutic point of view, the concept of the metabolic syndrome would bear a special interest if a unique common underlying cause, for all the constituents of the syndrome were to be identified. In the initial proposition of Reaven and in the WHO definition, insulin resistance was to be the common link. Epidemiological studies not only support this association in most cases, but also identify subgroups of individuals with normal insulin sensitivity who nevertheless fulfill the criteria for the metabolic syndrome [12].

Future research is still needed to evaluate the hypothesis underlying the novel IDF criteria, i.e., that visceral obesity is central to the syndrome Meanwhile, we still have to face an increasing number of individuals with visceral obesity, dyslipidemia, impaired glucose metabolism and high blood pressure. The simultaneous occurrence of several risk factors places these individuals at very high risk for the development of vascular diseases and diabetes mellitus. What can practically be done to prevent the apparition of such a high risk profile in our population, and to correct the abnormalities in affected individuals? Weight loss in obese or overweight subjects, and prevention of obesity at the population level, is certainly the prime objective to attain. There is huge evidence that, in rodents, dietary factors play a major role in the development of obesity and obesity-associated co-morbidities. Feeding a high fructose or high sucrose diet leads to increased visceral fat, insulin resistance, hyperglycemia and high blood pressure in rodents. These effects are relevant for humans too, since there is a growing concern regarding the increased consumption of sweetened snacks and beverages in western diets [13]. Similarly, diets rich in saturated fat cause metabolic alterations close to the metabolic syndrome in animal models [14]. On the contrary, in the same rodents models, supplementation with long chain n-3 fatty acids prevents or even reverses partially or completely the metabolic alterations characterizing the metabolic syndrome [15]. Epidemiological studies in natives of Alaska and Groenland also sustain the probable protecting role of such fatty acids from marine origin [16,17]. Clearly, both basic studies and intervention trials are required to further delineate which dietary change would be effective and how to implement it.

Dietary factors can clearly contribute to the development of the metabolic syndrome, or of each of its individual components. The role of other environmental factors, and more particularly of physical activity, should however not be neglected [18]. Changes in diet, aiming to reduce sugar and saturated fat consumption and promotion of physical activity are therefore primary goals in our effort to prevent and reduce metabolic disorders. However, one also has to acknowledge that most lifestyle intervention programs aiming to reduce weight and maintain a normal weight in obese subjects show a low level of success. In this regard, drug therapy may in the future show beneficial effects on body weight and associated morbidity, and may be of use to improve compliance and effectiveness of lifestyle intervention. The development of new pharmacological agents which promote visceral fat loss [19] or insulin sensitivity [20] and the development of effective surgical means to reduce weight [21] surely represent some hope. In this regard, studies will be required to evaluate not only the short-term effects of drug- or surgically- induced weight loss, but also their long-term effect on morbidity and mortality.

Table 1. Different Definitions of the Metabolic Syndrome


WHO, World Health Organization; NCEP/ATPIII, American National Cholesterol Programme; IDF, International Diabetes Federation; HDL, high density lipoprotein; BMI, body mass index.

REFERENCES

[1] Jonsson T, Ahren B, Pacini G, et al. A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs. Nutr Metab (Lond.) 2006; 3: 39.

[2] Stanton KR, Acs Z. The infrastructure of obesity and the obesity epidemic: implications for public policy. Appl Health Econ Health Policy 2005; 4: 139-46.

[3] Morabia A, Costanza MC. The obesity epidemic as harbinger of a metabolic disorder epidemic: trends in overweight, hypercholesterolemia, and diabetes treatment in Geneva, Switzerland, 1993-2003. Am J Public Health 2005; 95: 632-5.

[4] Li C, Ford ES, McGuire LC, Mokdad AH, Little RR, Reaven GM. Trends in hyperinsulinemia among nondiabetic adults in the U.S. Diabetes Care, 2006; 29: 2396-402.

[5] Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-607.

[6] Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). J Am Med Assoc 2001; 285: 2486-2497.

[7] World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation, part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization WHO/NCD/NCS/1999.

[8] Alberti KGMM, Zimmet P, Shaw J. The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059-1062.

[9] Hunt KJ, Resendez RG, Williams K, Haffner SM, Stern MP. San Antonio Heart Study. National Cholesterol Education Program versus World Health Organization metabolic syndrome in relation to all-cause and cardiovascular mortality in the San Antonio Heart Study. Circulation 2004; 110: 1251-7.

[10] Gale EAM. The myth of the metabolic syndrom. Diabetologia 2005; 48: 1679-1683.

[11] Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal. Joint statement from the American diabetes Qassociation and the european Association for the study of Diabetes. Diabetologia 2005; 48: 1684-1699.

[12] Hanley AJ, Williams K, Gonzalez C, et al. San Antonio Heart Study, Mexico City Diabetes Study, Insulin Resistance Atherosclerosis Study. Prediction of type 2 diabetes using simple measures of insulin resistance: combined results from the San Antonio Heart Study, the Mexico City Diabetes Study, and the Insulin Resistance Atherosclerosis Study. Diabetes 2003; 52:463-9.

[13] Le KA, Tappy L. Metabolic effects of fructose. Curr Opin Clin Nutr Metab Care 2006; 9:469-75.

[14] Samuel VT, Liu ZX, Qu X, et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-53.

[15] Delarue J, LeFoll C, Corporeau C, Lucas D. N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? Reprod Nutr Dev 2004; 44: 289-99.

[16] Ebbesson SO, Ebbesson LO, Swenson M, Kennish JM, Robbins DC. A successful diabetes prevention study in Eskimos: the Alaska Siberia project. Int J Circumpolar Health 2005; 64: 409-24.

[17] Ebbesson SO, Risica PM, Ebbesson LO, Kennish JM, Tejero ME. Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska Siberia project. Int J Circumpolar Health 2005; 64: 396-408.

[18] Jakicic JM, Otto AD. Physical activity considerations for the treatment and prevention of obesity. Am J Clin Nutr 2005; 82: 226S-229S.

[19] RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005; 3651389-97.

[20] Norkus A, Pirags V, Podar T, et al, Proactive investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the proactive study (Prospective pioglitazone clinical trial in macrovascular events): A randomised controlled trial. Lancet 2005; 3661279-89.

[21] Rubino F. Bariatric surgery: effects on glucose homeostasis. Curr Opin Clin Nutr Metab Care 2006; 9: 497-507.


Luc Tappy
(Guest Editor)
Department of Physiology
Lausanne University School of
Biology and Medicine
Lausanne, Switzerland
and Service of Nutrition
University Hospital Cavalle Blanche, Brest
France


Jacques Delarue, and Kim-Anne Lê
(Co-Editors)
Department of Physiology
Lausanne University School of
Biology and Medicine
Lausanne, Switzerland
and Service of Nutrition
University Hospital Cavalle Blanche, Brest
France

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Epidemics of Obesity and Metabolic Disorders: Are Dietary Fats or Sugars Involved?
George A. Bray and Barry M. Popkin

Epidemiologic investigations can provide insights to the diet-disease relationship in different populations. Slow but continual intake of small amounts of energy in excess of energy needs leads to obesity. Although experimental obesity in animals eating a low-fat diet is the exception, development of obesity in animals eating high-fat diets is the rule. Subjects who were placed on a low-fat diet lost weight, even when weight loss was not the goal of the study. The intake of carbohydrates as sugar and high fructose corn syrup in beverages may have detrimental health effects, since the compensation for oral intake of calorically sweetened beverages is inadequate. Low-carbohydrate diets appeared to produce more weight loss for the first 6 months but not thereafter.


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Pharmacological Treatment of Obesity, Food Intake, and Reversal of Metabolic Disorders
A.J. Scheen and N. Paquot

The present paper is reviewing the current place of weight-reducing drugs in the overall management of overweight/obese subjects, especially those with metabolic disorders and type 2 diabetes. Anti-obesity agents should be carefully evaluated in long-term (1-2 years) randomized controlled trials. Recent systematic reviews and meta-analysis assessed both the safety and efficacy of the two drugs currently used in the treatment of obesity, i.e. orlistat, a gastric and pancreatic lipase inhibitor that reduces fat absorption from the gut, and sibutramine, a combined norepinephrine and serotonin reuptake inhibitor that regulates food intake. Rimonabant, a new compound acting as selective blocker of CB1 receptors of the endocannabinoid system, raises much interest as it promotes weight reduction by a central effect and also exerts peripheral effects targeting cardiometabolic risk. Special attention will be paid to beneficial metabolic effects resulting from (even moderate) weight loss and to possible additional effects beyond weight reduction.


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Dietary Factors in Childhood Obesity
Patrick Tounian

Obesity is a disease that combines the influence of a genetic predisposition with an obesogenic environment. Our purpose is to review the role of dietary factors in the developement and the maintenance of obesity in children, and to point out the alterations of energy balance induced by energy restriction. There is considerable evidence that a genetic susceptibility to fat gain is necessary to override the regulatory systems of energy intake. Therefore, only children highly sensitive to the abundant palatable food in the environment can develop obesity. The current way of life in industrialized countries, but also the socioeconomic development of urban areas in transitional nations, provide such a condition. Despite conflicting results in the literature, obese children must have increased energy intake in order to match their enhanced energy expenditure. Extra-prandial intake and higher proportion of energy intake during the second part of the day contribute to a positive energy balance, although these food intake patterns are not specific to obese children. Similarly, whatever the relative proportion of fat or carbohydrate intake, an excess in total energy intake is an absolute requisite to lead to weight gain. The discrepancies about the role of food portion size and energy density, sugar-sweetened drinks, added sugars and high-glycemic index meals in the development and the maintenance of childhood obesity are discussed. The compensatory mechanisms which offset the effects of diet, explaining the poor therapeutic results of the treatment, will also be dealt with. Further research focused on the genetic and metabolic control of food intake should be developed to curb the increasing prevalence of childhood obesity.


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Non-Alcoholic Fatty Liver Disease in Children
Papandreou Dimitrios, Rousso Israel and Mavromichalis Ioannis

The aim of this review is to summarize what is known about pediatric non-alcoholic fatty liver disease (NAFLD) in terms of prevalence, pathogenesis, diagnosis, histology and treatment. NAFLD is increasingly recognized as a major health burden in obese children. NAFLD is a spectrum, ranging from fatty infiltration of the liver alone (steatosis), which may lead to fatty infiltration with inflammation known as steatohepatitis or non alcoholic steatohepatitis (NASH) that is characterized by the potential to progress to fibrosis, cirrhosis and end stage liver disease. NASH is associated with obesity, diabetes, insulin resistance and hypertriglyceridemia. While the majority of individuals with risk factors like obesity and insulin resistance (IR) have steatosis, only a minority develop steatohepatitis. Although steatosis is a prerequisite for the definition of NAFLD in adults and children, distinct differences are often apparent in the extent or location of fat, inflammation and fibrosis. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising.


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Reversal of Diabetes and Metabolic Disorders After Bariatric Surgery
Melania Manco, Laura Leccesi and Geltrude Mingrone

Prevalence of morbid obesity is dramatically increasing over the world. The failure of medical and behavioural treatments has lead to the widespread development of surgical techniques for the resolution of morbid obesity and its co-morbidities. The present review highlights the effect of two of these techniques, the Roux-en-Y gastric bypass (RYGB) and the Biliopancreatic Diversion (BPD), on metabolic co-morbidities, which mainly include diabetes mellitus, non alcoholic fatty liver disease and polycystic ovary syndrome. Among the other bariatric techniques currently used, these above mentioned procedures result to be the most effective in obtaining a stable weight loss and the fully resolution of co-morbidities. They act by different mechanisms, which are largely still unidentified. The former is a restrictive technique, which causes a reduction in the alimentary flow. The latter induces a prevalent lipid malabsorption. Most Authors agree that surgery modifies the hormonal milieu, acting at several sites, which include the entero-insular axis, the muscle and the adipose tissues. Thereby, we examine the most significant studies performed in animals and humans aiming to compare changes in beta cell function and whole body glucose uptake following restrictive or malabsorptive surgery. Weighting the beneficial effects of bariatric surgery against short- and long-term complications, bariatric surgery seems to be the most effective therapy for severe obesity and type 2 diabetes mellitus.


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Can Marine Omega 3 Fatty Acids Prevent and/or Treat Metabolic Syndrome?
J. Delarue, V. Le Guen, G. Allain, C. Corporeau and S. Guillerm

The metabolic syndrome (MS) has a high prevalence in different countries (~ 10% in France). It associates in the same subject central obesity, decrease in HDL cholesterol, increase in plasma triglycérides, glucose intolerance and hypertension. Insulin-resistance is a common feature even though it has been excluded from the more recent definitions because of the difficulty to assess it in clinical practice. Physiopathology of MS is not univocal. Stress, insulin resistance, central obesity are concerned. Marine omega 3 fatty acids (EPA and DHA) have demonstrated in many studies in rodents and some studies in humans their potentiality to prevent and treat MS, by their insulin-sensitizing effect, their ability to modulate mental stress response, to decrease plasma triglycerides, to reduce lipotoxicity, to slow down atherogenesis, to decrease oxidative stress and to ameliorate endothelial dysfunction. Additional studies are required to definitively confirm their usefulness and define their optimal daily amount for prevention and treatment beside physical activity, maintenance or reduction of body weight and pharmacological therapy of specific components of MS.


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Physical Activity and Insulin Resistance
Guy Plasqui and Klaas R. Westerterp

Insulin resistance, often caused by excessive body weight, is a major risk factor for the development of type 2 diabetes and cardiovascular disease. Several studies have shown the beneficial effects of physical activity on insulin resistance. A single bout of physical activity, whether it is aerobic or resistance exercise, significantly improves insulin sensitivity up to 48h after a single exercise session. Both endurance and resistance exercise training lead to prolonged beneficial effects on insulin action. In addition, many studies have shown the inverse relation between a high daily physical activity level and insulin resistance and cardiovascular disease. Although one might argue about what type, frequency, intensity or duration of physical activity is the most beneficial, the real question at issue is how to implement physical activity into subjects’ daily life routines in order to achieve long-term, in essence lifetime improvements in their total daily physical activity level and hence insulin sensitivity. To maximise the chance of long-term success, subjects should be encouraged to be as physically active as possible, have a variety of activity options, build activities into their daily routines and develop an active lifestyle, rather than just following exercise prescriptions.


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Occurrence and Biological Properties of Sphingolipids – A Review
Karin Wehrmüller

Sphingolipids are a complex group of polar lipids. Variations in their components (backbone, polar head group and fatty acid) engenders a large and complex structural variety which affects the biological properties of the individual molecules. Sphingolipids are omnipresent in foodstuffs, can cross the intestinal barrier and are biologically active. The quantities in food range from a few µg/kg in fruits and some vegetables up to 1 g/kg in milk products, eggs, meat and soybeans. Several positive impacts of sphingolipids on human health have been described: In vitro experiments measuring the antibacterial properties of sphingolipids have been successfully carried out. A sphingolipid-enriched diet showed inhibitory effects on the formation of early colon carcinoma precursors (Aberrant Crypt Foci (ACF)) in mice. Sphingolipid metabolites also induce apoptosis in transformed human cell cultures. Taken together, there is a high probability that sphingolipids have anticancerogenic properties in humans. Finally, a specific group of sphingolipids is essential for the maintenance of nerve function and structure and the enrichment of sphingomyelin in a cholesterol-rich diet successfully reduces cholesterol absorption. Although sphingolipids are probably not essential dietary components, they can significantly contribute to human health.

This article reviews the present state of knowledge concerning the occurrence and biological properties of sphingolipids.


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Olive Oil and Haemostasis
Javier Delgado-Lista, Jose Lopez-Miranda, Pablo Perez-Martinez, Juan Ruano, Francisco Fuentes and Francisco Perez-Jimenez

Olive oil is the keystone of the Mediterranean diet, and is its most characteristic food. More than 80% of the visible fat of this diet is consumed in the form of olive oil, which is almost the only source of fat, employed both in cooking (stir-frying, deep frying) and as a dressing.

In spite of the great importance of olive oil in the Mediterranean diet, many of the properties of some of its components remain unclear.

It has already been shown that olive oil has a wide range of healthy properties, including the reduction of LDL cholesterol in comparison with diets high in saturated fatty acids (SAFA), control of blood pressure, the lowering of inflammation markers, as well as beneficial effects on certain types of cancer and cardiovascular disease and age-related cognitive decline [1-4].