Omega-6 polyunsaturated fatty acids and the early origins of obesity

PURPOSE OF REVIEW: The incidence of obesity and its related metabolic disorders has increased significantly over the past 3 decades, culminating in the current global epidemic of metabolic disease and leading to the search for contributing factors. Exposure of the developing foetus/neonate to a typical Western diet increases their risk of obesity and metabolic disorders throughout the life-course, creating an intergenerational cycle of metabolic disease. In Western countries, this epidemic of metabolic disease has coincided with a marked increase in the intake of omega-6 polyunsaturated fatty acids (omega-6 PUFA), leading to suggestions that the two may be causally related. RECENT FINDINGS: Recent studies have emphasized the proadipogenic properties of the omega-6 PUFA, and provided evidence that rodents fed on diets with omega-6 PUFA contents similar to the typical US diet (6–8% energy) have an increased fat mass. Importantly, recent studies have shown that perinatal exposure to a high omega-6 PUFA diet results in a progressive accumulation of body fat across generations. SUMMARY: This review highlights the recent evidence supporting the role of the omega-6 PUFA in the early life origins of obesity and metabolic disease, the need for more clinical studies and the potential need for health agencies to re-evaluate current recommendations to further increase omega-6 PUFA intakes.Beverly S. Muhlhausler and Gérard P. Ailhau

Prenatal programming of postnatal obesity: fetal nutrition and the regulation of leptin synthesis and secretion before birth

Exposure to either an increased or decreased level of intrauterine nutrition can result in an increase in adiposity and in circulating leptin concentrations in later life. In animals such as the sheep and pig in which fat is deposited before birth, leptin is synthesised in fetal adipose tissue and is present in the fetal circulation throughout late gestation. In the sheep a moderate increase or decrease in the level of maternal nutrition does not alter fetal plasma leptin concentrations, but there is evidence that chronic fetal hyperglycaemia and hyperinsulinaemia increase fetal fat mass and leptin synthesis within fetal fat depots. Importantly, there is a positive relationship between the relative mass of the ‘unilocular’ component of fetal perirenal and interscapular adipose tissue and circulating fetal leptin concentrations in the sheep. Thus, as in the neonate and adult, circulating leptin concentrations may be a signal of fat mass in fetal life. There is also evidence that leptin can act to regulate the lipid storage, leptin synthetic capacity and potential thermogenic functions of fat before birth. Thus, leptin may act as a signal of energy supply and have a ‘lipostatic’ role before birth. Future studies are clearly required to determine whether the intrauterine and early postnatal nutrient environment programme the endocrine feedback loop between adipose tissue and the central and peripheral neuroendocrine systems that regulate energy balance, resulting in an enhanced risk of obesity in adult life.I. C. McMillen, B. S. Muhlhausler, J. A. Duffield and B. S. J. Yue

Novel insights, challenges and practical implications of DOHaD-omics research

Research investigating the developmental origins of health and disease (DOHaD) has never had the technology to investigate physiology in such a data-rich capacity and at such a microlevel as it does now.A symposium at the inaugural meeting of the DOHaD Society of Australia and New Zealand outlined the advantages and challenges of using "-omics" technologies in DOHaD research.DOHaD studies with -omics approaches to generate large, rich datasets were discussed.We discuss implications for policy and practice and make recommendations to facilitate successful translation of results of future DOHaD-omics studies.Nicolette A Hodyl and Beverly Muhlhausle

Effect of a maternal cafeteria diet on the fatty acid composition of milk and offspring red blood cells

Abstract not availableM.A. Vithayathil, J.R. Gugusheff, R.A. Gibson, Z.Y. Ong, B.S. Muhlhausle

Impact of maternal obesity on offspring adipose tissue: lessons for the clinic

Maternal obesity is a major risk factor for the subsequent development of obesity and Type, diabetes in the child. This relationship appears to be driven largely by the exposure of the fetus to an increased nutrient supply during critical periods of development, which results in persistent changes in the structure and function of key systems involved in the regulation of energy balance, appetite and fat deposition. One of the key targets is the fat cell, or adipocyte, in which prenatal overnutrition programs a heightened capacity for fat storage. The increasing prevalence of maternal obesity has led to an urgent need for strategies to break the resulting intergenerational cycle of obesity and metabolic disease. This review will discuss the relationship between maternal obesity and poor metabolic health of the offspring, with a particular focus on the involvement of adipose tissue, recent clinical studies examining potential strategies for intervention and priority areas for further research.Beverly S. Muhlhausler, and Mini A. Vithayathi

Naloxone treatment alters gene expression in the mesolimbic reward system in 'junk food' exposed offspring in a sex-specific manner but does not affect food preferences in adulthood

Abstract not availableJ.R. Gugusheff, Z.Y. Ong, B.S. Muhlhausle

The fatty acid composition of excreta of broiler chickens fed different dietary fatty acids

Published: October 15, 2017Background and Objective: Excreted fatty acids represent the net result of fat digestion, absorbtion and bioconversion by chickens or their intestinal microbiome and thus provide information on the capacity of the birds to utilize different fat types. This study aimed to clarify the relationship between the fatty acid profile of diet and excreta in broiler chickens. Materials and Methods: Male Cobb 500 broilers (n = 240) were fed (ad libitum) one of 6 different diets supplemented with 4% (w/w) beef tallow, flaxseed, corn, macadamia, canola or coconut oils (4 replicate pens/treatment) from hatching day. At day-40 post-hatch, excreta samples were collected for fatty acids analysis. Results: Significant positive linear correlations (R = 0.82-0.99) were found in the fatty acid content of diets and excreta for all fatty acid groups in all treatments. Comparing the individual fatty acid content of diet and excreta suggested that the broilers preferentially utilized (in decending order, if present) omega-3 polyunsaturated fatty acids, omega-9 and omega-7 monounsaturated fatty acids and most saturated fatty acids (except C16:0 and C18:0), but the omega-6 polyunsaturated fatty acids were under utilized even when they were the most abundant. Conclusion: Fat sources which are high in the C16:0, C18:0 and omega-6 fatty acids may not be ideal for broiler feed formulations for nutritional and economical reasons.Khaled Kanakri, John Carragher, Robert Hughes, Beverly Muhlhausler, Carolyn de Koning and Robert Gibso

Perinatal overnutrition and the programming of food preferences: pathways and mechanisms

One of the major contributing factors to the continuous rise in obesity rates is the increase in caloric intake, which is driven to a large extent by the ease of access and availability of palatable high-fat, high-sugar ‘junk foods’. It is also clear that some individuals are more likely to overindulge in these foods than others; however, the factors that determine an individual's susceptibility towards the overconsumption of palatable foods are not well understood. There is growing evidence that an increased preference for these foods may have its origins early in life. Recent work from our group and others has reported that in utero and early life exposure to these palatable foods in rodents increased the offspring's preference towards foods high in fat and sugar. One of the potential mechanisms underlying the programming of food preferences is the altered development of the mesolimbic reward system, a system that plays an important role in driving palatable food intake in adults. The aim of this review is to explore the current knowledge of the programming of food preferences, a relatively new and emerging area in the DOHAD field, with a particular focus on maternal overnutrition, the development of the mesolimbic reward system and the biological mechanisms which may account for the early origins of an increased preference for palatable foods.Z. Y. Ong, J. R. Gugusheff and B. S. Muhlhausle

The early origins of food preferences: targeting the critical windows of development

The nutritional environment to which an individual is exposed during the perinatal period plays a crucial role in determining his or her future metabolic health outcomes. Studies in rodent models have demonstrated that excess maternal intake of high-fat and/or high-sugar "junk foods" during pregnancy and lactation can alter the development of the central reward pathway, particularly the opioid and dopamine systems, and program an increased preference for junk foods in the offspring. More recently, there have been attempts to define the critical windows of development during which the opioid and dopamine systems within the reward pathway are most susceptible to alteration and to determine whether it is possible to reverse these effects through nutritional interventions applied later in development. This review discusses the progress made to date in these areas, highlights the apparent importance of sex in determining these effects, and considers the potential implications of the findings from rodent models in the human context.Jessica Rose Gugusheff, Zhi Yi Ong, and Beverly Sara Muhlhausle

A maternal 'junk-food' diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning

Perinatal exposure to a maternal “junk-food” diet has been demonstrated to increase the preference for palatable diets in adult offspring. We aimed to determine whether this increased preference could be attributed to changes in μ-opioid receptor expression within the mesolimbic reward pathway. We report here that mRNA expression of the μ-opioid receptor in the ventral tegmental area (VTA) at weaning was 1.4-fold (males) and 1.9-fold (females) lower in offspring of junk-food (JF)-fed rat dams than in offspring of dams fed a standard rodent diet (control) (P<0.05). Administration of the opioid antagonist naloxone to offspring given a palatable diet postweaning significantly reduced fat intake in control offspring (males: 7.7±0.7 vs. 5.4±0.6 g/kg/d; females: 6.9±0.3 vs. 3.9±0.5g/kg/d; P<0.05), but not in male JF offspring (8.6±0.6 vs. 7.1±0.5g/kg/d) and was less effective at reducing fat intake in JF females (42.2±6.0 vs. 23.1±4.1% reduction, P<0.05). Similar findings were observed for total energy intake. Naloxone treatment did not affect intake of standard rodent feed in control or JF offspring. These findings suggest that exposure to a maternal junk-food diet results in early desensitization of the opioid system which may explain the increased preference for junk food in these offspring.—Gugusheff, J. R., Ong, Z. Y., Muhlhausler, B. S. A maternal “junk-food” diet reduces sensitivity to the opioid antagonist naloxone in offspring postweaning.Jessica R. Gugusheff, Zhi Yi Ong and Beverly S. Muhlhausle