Review
Temporal changes in dietary fats: Role of n−6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity

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Abstract

The importance of a high fat intake in the increasing prevalence of childhood and adult obesity remains controversial. Moreover, qualitative changes (i.e. the fatty acid composition of fats) have been largely disregarded. Herein is reviewed the role of polyunsaturated fatty acids (PUFAs) of the n−6 series in promoting adipogenesis in vitro and favouring adipose tissue development in rodents during the gestation/suckling period. Epidemiological data from infant studies as well as the assessment of the fatty acid composition of mature breast milk and infant formulas over the last decades in the Western industrialized world are revisited and appear consistent with animal data. Changes over decades in the intake of n−6 and n−3 PUFAs, with a striking increase in the linoleic acid/α-linolenic ratio, are observed. In adults, using a consumption model based upon production data, similar changes in the PUFA content of ingested lipids have been found for France, and are associated with an increase of fat consumption over the last 40 years. These profound quantitative and qualitative alterations can be traced in the food chain and shown to be due to changes in human dietary habits as well as in the feeding pattern of breeding stock. If prevention of obesity is a key issue for future generations, agricultural and food industry policies should be thoroughly reevaluated.

Introduction

Both childhood and adult obesity can be considered a non-infectious epidemic. According to the childhood obesity working group of the International Obesity Task Force (2004) “the epidemic of European Union childhood obesity appears to be accelerating out of control. Things are worse than our gloomiest predictions”. As a result, cardiovascular risk factors are now becoming “routinely reported” among children in many populations. In adults, according to a recent report of WHO consultation on obesity, a continuous trend in overweight and obesity has also been observed in most industrialized countries. Of interest, in studies conducted in males and females (BMI > 30; age range ∼20–70 years), a significant upward shift in the prevalence figures occurred in USA, Canada and UK in the 1980–1990 period whereas in France, according to the WHO Monica project published in 2000, a similar shift was observed later, in the 1985–1995 period. These observations suggest important changes in various social trends favouring energy intake and decreasing energy expenditure among which sedentary lifestype appears as an important player. However, qualitative changes in food consumption have been largely ignored in the last 40 years despite dramatic changes in food habits and in the food chain, including the feeding pattern of breeding stock.

The role of dietary fat as a major player in adult human obesity has remained a controversial issue [1], [2] because the prevalence of overweight and obesity has increased dramatically over the last decades despite no recent major change in the amount of ingested fats. However, as we shall see, this conclusion needs to be reassessed. Moreover, the importance of qualitative changes in the fatty acid composition of fats has been largely disregarded despite a dramatic alteration over decades of the balance of essential polyunsaturated fatty acids (PUFAs). Since the sixties, indiscriminate recommendations have been made to substitute vegetable oils, (high in n−6 PUFAs and low in n−3 PUFAs), for saturated fats. Moreover, significant changes in animal feeds and the food chain have been introduced. For example, the n−6/n−3 PUFA ratios in food commonly consumed in the American diet range from 10 to 41, considerably above official recommendations. In the last 50 years, these changes have been accompanied by a significant increase in the supply of dietary arachidonic acid (ARA; 20:4 n−6). Of note, the amounts of ARA in the most consumed foods are significantly higher than those previously published [3]. Equally important, the requirement for linoleic acid (LA; 18:2 n−6) for growth and development as a precursor of arachidonic acid and its metabolites has been significantly overestimated [4] whereas the recommendation to reduce n−6 PUFAs even as the n−3 PUFAs are increased has not been followed [5]. Thus, in addition to a positive energy balance, qualitative changes in the fatty acid composition of ingested fats, including breast milk and formula milk, may help to gain insight in the increasing prevalence of overweight and obesity in children and adults which add to the cross-sectional and longitudinal studies showing an association between high fat intake and a subsequent fat mass enhancement [6], [7], [8], [9]. Evidence from animal and human studies discussed herein favour the possibility that changes in the balance of essential PUFAs are altering the early stages of adipose tissue development, i.e. during fetal life and infancy which are the periods showing the highest adaptability and vulnerability to external factors but also at the adult age during which adipose precursor cells remain present and potentially able to differentiate into adipocytes.

Section snippets

White adipose tissue development in early life and responses to dietary fats

How important is the development of white adipose tissue in early life? In humans, it is known that this tissue develops as early as the second trimester of pregnancy and more extensively during the last trimester in various sites (buccal, neck, shoulder, gluteal, perirenal) and after birth [10]. Adipocytes represent between one third and two thirds of the total number of cells in adipose tissue. The remaining cells present in the stromal-vascular fraction are various blood cells, endothelial

Adipogenesis and fatty acids as adipogenic hormones

Knowledge of adipogenesis has increased dramatically over the last two decades with the use of clonal and non-clonal adipose precursor cells from rodents and humans. Adipogenesis is a sequential process in which glucocorticoids, insulin and IGF-I have been identified as the major adipogenic hormones [15]. Both in rodents and humans, long-chain fatty acids act also at the precursor stage and enhance the formation of adipocytes. The first line of evidence that fatty acids (FA) are involved has

General considerations

As mentioned above, the importance of a high lipid intake in childhood obesity has been seriously challenged because of a lack of evidence for the increased energy intake as fat despite a striking increase in the prevalence of overweight and obesity among youths [59]. According to most investigators, physical inactivity is considered to be a major contributor to this alarming trend. However, distinct and important weight-related events appear to take place during pregnancy and at a very early

General considerations

In the last half century, physiological and biochemical effects of polyunsaturated fatty acids have been thoroughly investigated and are now better understood. As discussed above (see Section 3), changes in food practices are revealed by changes in the fatty acid (FA) composition of breast milk and adipose tissue lipids. Not surprisingly, various factors have changed over time, i.e. animal feed and food processing, leading to significant changes in the fatty acid composition of ingested fats.

Discussion

The prevalence of overweight and obesity has escalated dramatically during the last decades both in children and adults. This recent epidemic is not attributable to genetic factors as it occurred over a short period where substantial changes in population gene pools cannot be seen. Among environmental factors, physical inactivity associated to increased caloric intake, i.e. in practice to high-fat diets, plays an important role. However, in addition to a positive energy balance, our results

Acknowledgements

The authors wish to thank Dr. R. Arkowitz for careful review and Ms. G. Oillaux for outstanding secretarial assistance. The key scientific contribution over the years of Drs. R. Négrel, P. Grimaldi, E. Amri and C. Dani and that of many other distinguished investigators, is gratefully acknowledged. Dr. P. Guesnet wishes to dedicate his contribution to Dr. R.G. Jensen who inspires his studies on milk fat composition.

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