Meeting the global protein supply requirements of a growing and ageing population.

Human dietary patterns are a major cause of environmental transformation, with agriculture occupying ~ 50% of global land space, while food production itself is responsible for ~ 30% of all greenhouse gas emissions and 70% of freshwater use. Furthermore, the global population is also growing, such that by 2050, it is estimated to exceed ~ 9 billion. While most of this expansion in population is expected to occur in developing countries, in high-income countries there are also predicted changes in demographics, with major increases in the number of older people. There is a growing consensus that older people have a greater requirement for protein. With a larger and older population, global needs for protein are set to increase. This paper summarises the conclusions from a Rank Prize funded colloquium evaluating novel strategies to meet this increasing global protein need.

Extraction of protein from food waste: An overview of current status and opportunities.

The chief intent of this review is to explain the different extraction techniques and efficiencies for the recovery of protein from food waste (FW) sources. Although FW is not a new concept, increasing concerns about chronic hunger, nutritional deficiency, food security, and sustainability have intensified attention on alternative and sustainable sources of protein for food and feed. Initiatives to extract and utilize protein from FW on a commercial scale have been undertaken, mainly in the developed countries, but they remain largely underutilized and generally suited for low-quality products. The current analysis reveals the extraction of protein from FW is a many-sided (complex) issue, and that identifies for a stronger and extensive integration of diverse extraction perspectives, focusing on nutritional quality, yield, and functionality of the isolated protein as a valued recycled ingredient.

Fetal and neonatal exposure to trans-fatty acids impacts on susceptibility to atherosclerosis in apo E*3 Leiden mice.

Nutrition during pregnancy can impact on the susceptibility of the offspring to CVD. Postnatal consumption of trans-fatty acids (TFA), associated with partially hydrogenated vegetable oil (PHVO), increases the risk of atherosclerosis, whereas evidence for those TFA associated with ruminant-derived dairy products and meat remain equivocal. In this study, we investigate the impact of maternal consumption of dietary PHVO (P) and ruminant milk fat (R) on the development of atherosclerosis in their offspring, using the transgenic apoE*3 Leiden mouse. Dams were fed either chow (C) or one of three high-fat diets: a diet reflecting the SFA content of a 'Western' diet (W) or one enriched with either P or R. Diets were fed during either pregnancy alone or pregnancy and lactation. Weaned offspring were then transferred to an atherogenic diet for 12 weeks. Atherosclerosis was assessed as lipid staining in cross-sections of the aorta. There was a significant effect of maternal diet during pregnancy on development of atherosclerosis (P=0·013) in the offspring with those born of mothers fed R or P during pregnancy displaying smaller lesions that those fed C or W. This was not associated with changes in total or lipoprotein cholesterol. Continuing to feed P during lactation increased atherosclerosis compared with that seen in offspring of dams fed P only during pregnancy (P<0·001). No such effect was seen in those from mothers fed R (P=0·596) or W (P=901). We conclude that dietary TFA have differing effects on cardiovascular risk at different stages of the lifecycle.

Component analysis of nutritionally rich chloroplasts: recovery from conventional and unconventional green plant species.

A study of the literature indicates that chloroplasts synthesise a range of molecules, many of which have nutritional value for humans, but the nutritional credentials of chloroplasts recovered from plant cells are not established. Chloroplast-rich-fractions (CRFs) were prepared from green plant species and the macro- and micro-nutrient composition compared with the whole leaf materials (WLMs). The results indicated that, on a dry weight basis, CRF material from a range of green biomass was enriched in lipids and proteins, and in a range of micronutrients compared with the WLM. Vitamins E, pro-vitamin A, and lutein were all greater in CRF preparations. Of the minerals, iron was most notably concentrated in CRF. Spinach CRFs possessed the highest α-tocopherol [62 mg 100 g-1, dry weight (DW)], ß-carotene (336 mg 100 g-1 DW) and lutein (341 mg 100 g-1 DW) contents, whilst grass CRFs had the highest concentration of alpha-linolenic acid (ALA) (69.5 mg g-1). The higher concentrations of α-tocopherol, ß-carotene, lutein, ALA and trace minerals (Fe and Mn) in CRFs suggested their potential use as concentrated ingredients in food formulations deficient in these nutrients.

Saturated fatty acids and coronary heart disease risk: the debate goes on.

PURPOSE OF REVIEW: Recently published meta-analyses of cohort studies and randomized controlled trials (RCTs) have challenged the link between saturated fatty acid (SFA) intake and coronary heart disease (CHD) risk. This review considers the outcome of these studies in the context of other evidence. RECENT FINDINGS: Recent meta-analyses of cohort studies suggest that reducing SFA intakes has little impact on CHD risk when replaced by carbohydrates. The evidence for benefits on CHD risk of replacing SFA with unsaturated fatty acids in cohort studies is stronger and is also supported by data from a recent Cochrane analysis of RCTs of dietary SFA reduction and CHD risk. This review highlights the challenges of cohort studies involving diet because of the changing patterns of dietary behaviour and other multifactorial risk factors. The studies included are normally conducted over many years and are often dependent on a single measurement of dietary intake. SUMMARY: The link between SFA intake, plasma cholesterol, and CHD risk is based on a broad range of evidence including mechanistic studies, RCTs of surrogate end points and clinical outcomes, as well as multinational population comparisons. Public health nutrition policy should continue to take into account the totality of evidence with recognition of the limitations of dietary cohort studies.

Anaerobic digestion of spring and winter wheat: Comparison of net energy yields.

Anaerobic digestion of wheat was investigated under batch conditions. The article compares the potential net energy yield between a winter wheat (sown in the autumn) and a spring wheat (sown in the spring) grown in the same year and harvested at the same growth stage in the same farm. The spring wheat had a slightly higher biochemical methane potential and required lower energy inputs in cultivation, but produced a lower dry biomass yield per hectare, which resulted in winter wheat providing the best overall net energy yield. The difference was small; both varieties gave a good net energy yield. Spring sowing may also offer the opportunity for growing an additional over-winter catch crop for spring harvest, thus increasing the overall biomass yield per hectare, with both crops being potential digester feedstocks.

In vitro determination of the protein quality of maize varieties cultivated in Malawi using the INFOGEST digestion method.

There is an urgent need to alleviate protein deficiencies in low-income countries where cereal-based diets dominate. The objective of this study was to use the INFOGEST static digestion method and a recently established analytical workflow to determine the in vitro amino acid digestibility and protein quality of seven maize varieties grown in Malawi. Protein quality was measured using the in vitro digestible indispensable amino acid score (DIAAS). Amino acid digestibility was higher for the dehulled, low fibre, provitamin A maize flour (66%), compared to whole grain maize flours (51-61%), suggesting that the presence of fibre reduced digestibility (p < 0.05). Lysine was the limiting amino acid in all varieties, with the following DIAAS values for each variety; Provitamin A maize - 24, SC 719 - 32, Mtsikinya - 37, SC 167 - 39, Quality protein maize (QPM) - 40, Bantum - 40, SC 403 - 44. In addition to the variety of maize, protein quality was dependent on the level of processing and the agronomic practice applied with higher protein quality for the SC 403 variety in which zinc enriched fertilizer was applied. Comparing protein quality data with published in vivo data showed that DIAAS data were in closer agreement than amino acid digestibility data, which was slightly lower than published values, with mean in vitro amino acid digestibilities of 56-70% compared to a mean in vivo value of 77%. Overall, the in vitro method was able to correctly predict both the direction and magnitude of response. The INFOGEST digestion method coupled with the new analytical workflow will therefore be useful in the screening of high protein cereal crops and subsequent development of cereal-based foods with high protein quality.

Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison with healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human-induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis, and molecular expression arrays. Results: We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion than wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. Conclusions: We have identified and characterised a rare causal variant in MTTP, and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinaemia. Our findings provide insights into mechanisms driving progressive NAFLD. Impact and Implications: A rare genetic variant in the gene MTTP has been identified as responsible for the development of severe non-alcoholic fatty liver disease in a four-generation family with no typical disease risk factors. A cell line culture created harbouring this variant gene was characterised to understand how this genetic variation leads to a defect in liver cells, which results in accumulation of fat and processes that promote disease. This is now a useful model for studying the disease pathways and to discover new ways to treat common types of fatty liver disease.

Limited Supply of Protein and Lysine Is Prevalent among the Poorest Households in Malawi and Exacerbated by Low Protein Quality.

We estimated dietary supplies of total and available protein and indispensable amino acids (IAAs) and predicted the risk of deficiency in Malawi using Household Consumption and Expenditure Survey data. More than half of dietary protein was derived from cereal crops, while animal products provided only 11%. The supply of IAAs followed similar patterns to that of total proteins. In general, median protein and IAA supplies were reduced by approximately 17% after accounting for digestibility, with higher losses evident among the poorest households. At population level, 20% of households were at risk of protein deficiency due to inadequate available protein supplies. Of concern was lysine supply, which was inadequate for 33% of households at the population level and for the majority of the poorest households. The adoption of quality protein maize (QPM) has the potential to reduce the risk of protein and lysine deficiency in the most vulnerable households by up to 12% and 21%, respectively.

Mapping brain activity of gut-brain signaling to appetite and satiety in healthy adults: A systematic review and functional neuroimaging meta-analysis.

Understanding how neurohormonal gut-brain signaling regulates appetite and satiety is vital for the development of therapies for obesity and altered eating behavior. However, reported brain areas associated with appetite or satiety regulators show inconsistency across functional neuroimaging studies. The aim of this study was to systematically assess the convergence of brain regions modulated by appetite and satiety regulators. Twenty-five studies were considered for qualitative synthesis, and 14 independent studies (20-experiments) found eligible for coordinate-based neuroimaging meta-analyses across 212 participants and 123 foci. We employed two different meta-analysis approaches. The results from the systematic review revealed the modulation of insula, amygdala, hippocampus, and orbitofrontal cortex (OFC) with appetite regulators, where satiety regulators were more associated with caudate nucleus, hypothalamus, thalamus, putamen, anterior cingulate cortex in addition to the insula and OFC. The two neuroimaging meta-analyses methods identified the caudate nucleus as a key area associated with satiety regulators. Our results provide quantitative brain activation maps of neurohormonal gut-brain signaling in heathy-weight adults that can be used to define alterations with eating behavior.

The Response of the Human Umbilical Vein Endothelial Cell Transcriptome to Variation in Magnesium Concentration.

Vascular endothelial cells have a critical role in the maintenance of cardiovascular function. Evidence suggests that endothelial function may be compromised under conditions of magnesium deficiency, which increases vulnerability to inflammation. Whole genome transcription analysis was used to explore the acute (24 h) effects of magnesium on human umbilical vascular endothelial cells (HUVEC) cultured in low (0.1 mM) or high (5 mM) concentrations. With low magnesium 2728 transcripts were differentially expressed compared to the 1 mM control cultures and 3030 were differentially expressed with high magnesium. 615 transcripts were differentially expressed under both conditions, of which only 34 showed a concentration-dependent response. Analysis indicated that cellular organisation and biogenesis and key cellular processes such as apoptosis were impacted by both low and high conditions. High magnesium also influenced protein binding functions, intracellular signal transduction, metabolic and catalytic processes. Both conditions impacted on stress-related processes, in particular the inflammatory response. Key mediators of calcium-dependent regulation of gene expression were responsive to both high and low magnesium conditions. The HUVEC transcriptome is highly sensitive to acute changes in the concentration of magnesium in culture medium. The findings of this study support the view that whilst inflammation is an important process that is responsive to magnesium, the function of the endothelium may be impacted by other magnesium-induced changes including maintenance of cellular integrity, receptor expression and metabolic functions. The high proportion of transcripts that did not show a concentration-dependent response suggests variation in magnesium may elicit indirect changes, possibly mediated by other ions.

A Comparison of Primary Human Hepatocytes and Hepatoma Cell Lines to Model the Effects of Fatty Acids, Fructose and Glucose on Liver Cell Lipid Accumulation.

Non-alcoholic fatty liver disease (NAFLD) begins with lipid accumulation within hepatocytes, but the relative contributions of different macronutrients is still unclear. We investigated the impact of fatty acids, glucose and fructose on lipid accumulation in primary human hepatocytes (PHH) and three different cell lines: HepG2 (human hepatoblastoma−derived cell line), Huh7 (human hepatocellular carcinoma cell line) and McA-RH7777 (McA, rat hepatocellular carcinoma cell line). Cells were treated for 48 h with fatty acids (0 or 200 µM), glucose (5 mM or 11 mM) and fructose (0 mM, 2 mM or 8 mM). Lipid accumulation was measured via Nile Red staining. All cell types accumulated lipid in response to fatty acids (p < 0.001). PHH and McA, but not HepG2 or Huh7 cells, accumulated more lipid with 11 mM glucose plus fatty acids (p = 0.004, fatty acid × glucose interaction, for both), but only PHH increased lipid accumulation in response to fructose (p < 0.001). Considerable variation was observed between PHH cells from different individuals. Lipid accumulation in PHH was increased by insulin (p = 0.003) with inter-individual variability. Similarly, insulin increased lipid accumulation in both HepG2 and McA cells, with a bigger response in McA in the presence of fatty acids (p < 0.001 for fatty acid × insulin). McA were more insulin sensitive than either HepG2 or Huh7 cells in terms of AKT phosphorylation (p < 0.001 insulin × cell type interaction). Hence, glucose and fructose can contribute to the accumulation of lipid in PHH with considerable inter-individual variation, but hepatoma cell lines are not good models of PHH.

Effects of omega-3 and -6 polyunsaturated fatty acids on ovine follicular cell steroidogenesis, embryo development and molecular markers of fatty acid metabolism.

We previously reported increased follicular fluid progesterone (P(4)) concentrations in ewes fed an n-3 compared to an n-6 polyunsaturated fatty acid (PUFA)-enriched diet, but detected no differential effect of n-3 and n-6 PUFA-enriched high-density lipoproteins (HDL) on granulosa cell (GC) steroidogenesis in vitro. Moreover, net n-6 PUFA-enriched HDL reduced early embryo development, but in the absence of a net uptake of FA. Consequently, we hypothesised that a) effects of n-3 PUFA on ovarian steroidogenesis are mediated by theca rather than GCs and b) during embryo culture lipids are acquired solely from the albumin fraction of serum, so that albumin-delivered n-3 and n-6 PUFA exert a greater differential effect on embryo development than either low-density lipoprotein (LDL)- or HDL-delivered PUFA. Data confirmed that n-3 PUFA increases P(4) production solely in theca cells and that this is associated with an increase in STAR transcript expression. Furthermore, LDL- and HDL-delivered n-3 PUFA are equally efficacious in this regard during the first 96 h of culture, but thereafter only HDL-delivered n-3 PUFA induces this effect in partially luteinised theca cells. We also demonstrate that albumin is the sole serum fraction that leads to a net uptake of FA during embryo culture. PUFA-enriched serum and albumin increased the yield of morphologically poorer quality blastocysts with increased transcript expression for the antioxidant enzyme SOD1. Important differential effects of n-3 and n-6 PUFA on ovarian steroidogenesis acting solely on theca cells are identified, but differential effects of PUFA on embryo development are less apparent.

Differential effects of the trans-18:1 isomer profile of partially hydrogenated vegetable oils on cholesterol and lipoprotein metabolism in male F1B hamsters.

Trans-fatty acid consumption from partially hydrogenated vegetable oil (PHVO) has been positively associated with multiple cardiovascular disease risk factors and events. This study was designed to examine the effects of trans-fatty acid isomer profile of PHVO on plasma lipids and lipoproteins and hepatic expression of key genes involved in cholesterol and fatty acid metabolism. Thirty-three male F(1)B strain Syrian Golden Hamsters were allocated to 1 of 3 hypercholesterolemic diets containing (5% by weight): 1) tristearin [control fat (CON)]; 2) partially hydrogenated high-oleic acid sunflower oil (PH-SUN); or 3) partially hydrogenated high-linoleic acid safflower oil (PH-SAF). PH-SUN contained more trans-4 to trans-10 18:1 compared with PH-SAF, which contained more trans-11 to trans-16 18:1. The addition of both PHVO to the diet increased plasma total cholesterol concentrations relative to CON, but only PH-SUN increased the plasma ratio of non-HDL:HDL cholesterol compared with CON. PH-SUN increased VLDL (total, large, and medium) and IDL particle concentrations while decreasing total, medium, and small HDL particle concentrations relative to CON. Both PHVO diets increased the hepatic cholesterol ester concentration, whereas the hepatic TG concentration was lower in PH-SUN compared with PH-SAF and CON. Levels of hepatic LDL receptor, HMG-CoA reductase, and sterol response element binding protein 1 mRNA were specifically reduced in the PH-SUN group compared to the CON group. Expression of SREBP1c was upregulated in both PHVO groups compared to CON, whereas only the PH-SAF group had higher levels of the lipogenic enzymes acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase-1 compared to CON. These results indicate that differences in the trans-fatty acid profile of PHVO can differentially affect lipid and lipoprotein metabolism.

Role of novel protein sources in sustainably meeting future global requirements.

Global population growth, increased life expectancy and climate change are all impacting world's food systems. In industrialised countries, many individuals are consuming significantly more protein than needed to maintain health, with the majority being obtained from animal products, including meat, dairy, fish and other aquatic animals. Current animal production systems are responsible for a large proportion of land and fresh-water use, and directly contributing to climate change through the production of greenhouse gases. Overall, approximately 60% of the global protein produced is used for animal and fish feed. Concerns about their impact on both human, and planetary health, have led to calls to dramatically curb our consumption of animal products. Underutilised plants, insects and single-cell organisms are all actively being considered as alternative protein sources. Each present challenges that need to be met before they can become economically viable and safe alternatives for food or feed. Many plant species contain anti-nutritional factors that impair the digestion and absorption of protein and micronutrients. Insects represent a potentially rich source of high-quality protein although, questions remain relating to digestibility, allergenicity and biosecurity. Algae, fungi and bacteria are also a rich source of protein and there is growing interest in the development of 'cultured meat' using stem cell technology. For the foreseeable future, it appears likely that the 'protein-economy' will remain mixed. The present paper reviews progress and future opportunities in the development of novel protein sources as food and animal feed.

Insects: A Potential Source of Protein and Other Nutrients for Feed and Food.

Sustainable production of healthy food for a growing global population, in the face of the uncertainties of climate change, represents a major challenge for the coming decade. Livestock provide food with high nutritional value but are frequently fed on human-edible crops and are associated with significant production of greenhouse gases. Recent years have seen increasing interest in the farming of insects as a sustainable source of human food, or as a replacement of ingredients such as soya or fishmeal in the feeds of terrestrial livestock or fish. This review provides an overview of insect physiology and growth regulation, considers the requirements for insect farming and mass production, and summarizes the nutritional value of the 10 most commonly studied insect species, before reviewing the literature on the use of insects as feed and food. We highlight the challenges required to develop a sustainable, safe, and affordable insect farming industry.

Combined innovations in public policy, the private sector and culture can drive sustainability transitions in food systems.

Global food system analyses call for an urgent transition to sustainable human diets but how this might be achieved within the current global food regime is poorly explored. Here we examine the factors that have fostered major dietary shifts across eight countries in the past 70 years. Guided by transition and food-regime theories, we draw on data from diverse disciplines, reviewing post-World War 2 shifts in consumption of three food commodities: farmed tilapia, milk and chicken. We show that large-scale shifts in commodity systems and diets have taken place when public-funded technological innovation is scaled-up by the private sector under supportive state and international policy regimes, highlighting pathways between commodity systems transformation and food-system transitions. Our analysis suggests that the desired sustainability transition will require public policy leadership and private-sector technological innovation alongside consumers who culturally value and can afford healthy, sustainable diets.

Are current dietary guidelines relevant to subjects on cholesterol-lowering drugs?

The present paper reviews the evidence as to whether patients on lipid-lowering drugs should restrict dietary SFA intake. Premature mortality from atherosclerotic CVD has fallen dramatically in many high-income countries. This appears to be due to a combination of improved treatment following a cardiovascular event and reduced risk factors, including LDL-cholesterol. Whether this reduction is due to changes in dietary habits, or the increasing availability of highly potent cholesterol-reducing drugs remains to be firmly established. While reducing dietary SFA intake has been the cornerstone of public health nutrition policy for several decades, the efficacy of such dietary changes has been challenged in recent years. While there remains a lack of consensus in the literature, there is an emerging view that dietary advice should be specifically modified to emphasise replacing SFA with PUFA in the diet rather than carbohydrate. The advice to moderate dietary SFA intake given to the general population is usually also given to those individuals at high risk of CVD who are prescribed lipid-lowering drugs. There is limited evidence to suggest that any potential benefit of such a diet on LDL-cholesterol may be offset by a concurrent decrease in HDL-cholesterol. However, as diets rich in SFA are frequently energy-dense, and rich in red and processed meat (potential risk factors for CVD in themselves), it would seem prudent to continue to advise patients on lipid-lowering drugs to maintain a low-fat diet.

A novel liver specific isoform of the rat LAR transcript is expressed as a truncated isoform encoded from a 5'UTR located within intron 11.

BACKGROUND: The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage. RESULTS: Using 5'RACE, we identified a 5'UTR within intron 11 of the rat LAR gene. We demonstrated that this gives rise to a novel isoform of the LAR transcript encoded from the identified region within intron 11. By priming across the site from exon 11 to exon 15 we show that the novel 5'UTR is not represented in the full-length transcript and thus, it produces a truncated form of the LAR mRNA. We examined the tissue distribution of this novel isoform and found it to be exclusively expressed in liver. We additionally identified a liver specific 150 kDa band with western blotting which we propose may represent the protein product of the novel transcript. Luciferase assays showed the region immediately upstream of the 5'UTR to possesses considerable promoter activity and that this may be conferred by the presence of a number of putative binding sites for liver enriched transcription factors. CONCLUSION: In summary, we describe a novel, liver specific, truncated isoform of the LAR transcript transcribed under the control of an intronic promoter, potentially representing a previously unidentified modulator of hepatic insulin signalling.