The effects of meat consumption on global health.

Meat represents an important source of high-quality dietary protein for a large proportion of the global population. In addition, red meat, in particular, significantly contributes to the intake of a wide range of micronutrients, including iron, zinc, selenium, vitamin D and vitamin B12. While these nutrients can be supplied in sufficient amounts by consumption of a range of fruit and vegetables, in many developing countries, where the availability of such foods may be limited, access to meat often protects against malnutrition and improves child cognitive development. Excessive consumption of meat and meat products is often associated with overconsumption of energy and fat, resulting in excess weight, obesity and an increased risk of chronic diseases, such as cardiovascular disease and type 2 diabetes. In addition, certain components of fresh and processed red meat may further increase the risk of these diseases and predispose the consumer to cancer, particularly colorectal cancer. In the face of population growth and global warming, there is increasing concern about the sustainability of farm animal production. Thus, while a modest intake of meat represents an important strategy to avoid essential nutrient deficiencies, limiting its intake can reduce the development of a range of chronic diseases and could have significant beneficial effects on global food security.

Pour une grande majorité de la population mondiale, la viande est une source importante de protéines de qualité. En particulier, la viande rouge contient divers micronutriments essentiels, dont le fer, le zinc, le sélénium, la vitamine D et la vitamine B12. Ces nutriments sont certes présents dans de nombreux fruits et légumes mais la disponibilité de ces aliments est souvent limitée dans les pays en développement, de sorte que c'est la consommation de viande qui permet de lutter contre la malnutrition et qui contribue au développement cognitif des enfants. D'un autre côté, une consommation excessive de viande et de produits carnés est fréquemment associée à une surconsommation de lipides et de protéines, avec pour effets une surcharge pondérale voire de l'obésité et un risque accru de maladies chroniques, dont les maladies cardiovasculaires et le diabète de type 2. En outre, certaines composantes de la viande rouge fraîche ou transformée majorent les risques associés à ces maladies ainsi que celui de développer un cancer, notamment colorectal. Compte tenu de la croissance de la population mondiale et du réchauffement climatique, la durabilité de la production animale est une question de plus en plus préoccupante. Par conséquent, si la consommation de viande en faibles quantités est une stratégie efficace pour lutter contre les carences en nutriments essentiels, le fait de limiter cette consommation permet de réduire l'exposition à plusieurs maladies chroniques et pourrait avoir un impact positif significatif sur la sécurité alimentaire à l'échelle mondiale.

La carne constituye una importante fuente de proteínas alimentarias de gran calidad para una enorme proporción de la población mundial. Además, la carne roja, en particular, contribuye en gran medida a la adquisición de muy diversos micronutrientes, sobre todo hierro, zinc, selenio, vitamina D y vitamina B12 y, si bien es posible obtener estos nutrientes ingiriendo cantidades suficientes de diversas frutas y hortalizas, en muchos países en desarrollo, donde este tipo de alimentos a veces escasea, la posibilidad de consumir carne suele proteger de la malnutrición y mejorar el desarrollo cognitivo del niño. Un consumo excesivo de carne y productos cárnicos suele acarrear una aportación excesiva de energía y grasas, lo que se traduce en sobrepeso, obesidad y un mayor riesgo de enfermedades crónicas como las cardiovasculares o la diabetes de tipo 2. Además, ciertos componentes de la carne roja fresca o procesada pueden elevar el riesgo de padecer estas dolencias y predisponer al consumidor al cáncer, en particular el colorrectal. Ante el crecimiento demográfico y el calentamiento planetario, cada vez preocupa más la cuestión de la sostenibilidad de la producción de animales de granja. Así pues, a la vez que un consumo modesto de carne constituye un importante expediente para evitar carencias en nutrientes esenciales, el hecho de limitar la ingesta puede reducir la aparición de toda una serie de enfermedades crónicas y podría tener efectos muy positivos en la seguridad alimentaria mundial.

Maternal high-fat feeding in pregnancy programs atherosclerotic lesion size in the ApoE*3 Leiden mouse.

Periods of rapid growth seen during the early stages of fetal development, including cell proliferation and differentiation, are greatly influenced by the maternal environment. We demonstrate here that over-nutrition, specifically exposure to a high-fat diet in utero, programed the extent of atherosclerosis in the offspring of ApoE*3 Leiden transgenic mice. Pregnant ApoE*3 Leiden mice were fed either a control chow diet (2.8% fat, n=12) or a high-fat, moderate-cholesterol diet (MHF, 19.4% fat, n=12). Dams were fed the chow diet during the suckling period. At 28 days postnatal age wild type and ApoE*3 Leiden offspring from chow or MHF-fed mothers were fed either a control chow diet (n=37) or a diet rich in cocoa butter (15%) and cholesterol (0.25%), for 14 weeks to induce atherosclerosis (n=36). Offspring from MHF-fed mothers had 1.9-fold larger atherosclerotic lesions (P<0.001). There was no direct effect of prenatal diet on plasma triglycerides or cholesterol; however, transgenic ApoE*3 Leiden offspring displayed raised cholesterol when on an atherogenic diet compared with wild-type controls (P=0.031). Lesion size was correlated with plasma lipid parameters after adjustment for genotype, maternal diet and postnatal diet (R 2=0.563, P<0.001). ApoE*3 Leiden mothers fed a MHF diet developed hypercholesterolemia (plasma cholesterol two-fold higher than in chow-fed mothers, P=0.011). The data strongly suggest that maternal hypercholesterolemia programs later susceptibility to atherosclerosis. This is consistent with previous observations in humans and animal models.

Synergism between cAMP and PPARγ Signalling in the Initiation of UCP1 Gene Expression in HIB1B Brown Adipocytes.

Expression of the brown adipocyte-specific gene, uncoupling protein 1 (UCP1), is increased by both PPARγ stimulation and cAMP activation through their ability to stimulate the expression of the PPAR coactivator PGC1α. In HIB1B brown preadipocytes, combination of the PPARγ agonist, rosiglitazone, and the cAMP stimulator forskolin synergistically increased UCP1 mRNA expression, but PGC1α expression was only increased additively by the two drugs. The PPARγ antagonist, GW9662, and the PKA inhibitor, H89, both inhibited UCP1 expression stimulated by rosiglitazone and forskolin but PGC1α expression was not altered to the same extent. Reporter studies demonstrated that combined rosiglitazone and forskolin synergistically activated transcription from a full length 3.1 kbp UCP1 luciferase promoter construct, but the response was only additive and much reduced when a minimal 260 bp proximal UCP1 promoter was examined. Rosiglitazone and forskolin in combination were able to synergistically stimulate promoters comprising of tandem repeats of either PPREs or CREs. We conclude that rosiglitazone and forskolin act together to synergistically activate the UCP1 promoter directly rather than by increasing PGC1α expression and by a mechanism involving cross-talk between the signalling systems regulating the CRE and PPRE on the promoters.

Operation and recovery of a seasonally-loaded UK waste stabilisation pond system.

An intermittent discharge waste stabilisation pond system was trialled for treatment of a seasonal wastewater load from a campsite. The system showed rapid acclimatisation to incoming load, with chlorophyll-a exceeding 700 mg l(-1) within 2 weeks and filtered and unfiltered effluent biochemical oxygen demand below 20 and 30 mg l(-1) respectively. Good performance continued for some weeks, after which photosynthetic oxygenation capacity in the first pond was seriously impaired by a shock loading believed to include fatty material. Inflow to the system was suspended and a surface film was broken up, after which the pond recovered within an 8-day period. Laboratory experiments indicated that interventions such as artificial aeration and dilution with effluent had no beneficial effect although mixing may have increased the rate of recovery.

Dietary fatty acids and cardiovascular disease.

In 1991, the Committee on Medical Aspects of Food Policy produced a report on the dietary reference values for food energy and nutrients for groups of people in the United Kingdom. The resulting recommendations, which included specific limits for intakes of total, saturated, trans- and cis-polyunsaturated fatty acids (PUFA) have remained a cornerstone of public health policy ever since, and similar recommendations have been adopted by the World Health Organization. These recommendations were made largely on the basis of specific effects of these fatty acids on the risk of developing atherosclerotic cardiovascular disease (CVD). The intervening years have seen a plethora of human epidemiological and intervention trials to further elucidate the specific relationship between dietary fatty acid intake, plasma lipids and lipoproteins and cardiovascular morbidity and mortality. A number of recent meta-analyses and systematic reviews have revisited the role of specific dietary fatty acid classes and CVD risk. In general, these continue to support a link between saturated fatty acids (SFA) and CVD morbidity/mortality. They also highlight the potent adverse effects of trans fatty acids derived from partially hydrogenated vegetable oil. The most recent data suggest that replacing SFA with cis-PUFA (primarily linoleic acid) has the greatest impact on reducing CVD risk. Evidence of specific beneficial effects of n-3 PUFA is generally stronger for secondary, rather than primary, CVD risk, and it is restricted to very long chain fatty acids of marine origin as opposed to alpha-linolenic acid. Taken together, these data suggest that recent focus on dietary n-6-to-n-3 PUFA ratios may have been misguided, and that future strategies should focus on replacing dietary SFA with total PUFA, rather than concentrating on n-6 : n-3 PUFA ratio.

The usability of digestate in organic farming.

As organic farming prohibits the use of synthetic fertilisers, animal slurries and manures must be used. Digestate offers an alternative to these and this study reports on three experiments conducted to determine its usability in terms of: (1) the effect on earthworm populations, (2) its fertilising effects on Italian Ryegrass and wild Creeping Thistle, and (3) the suppression effects digestate has on weed emergence. The results for digestate application to field plots were intermediate between slurry and no treatment for earthworm attraction and wild thistle suppression. In glasshouse trials it led to increased ryegrass growth compared with undigested slurry. Analysis showed that the digestate had improved nitrogen availability, leading to increased plant growth, but a reduced organic matter content compared with the slurry, leading to a positive though less beneficial impact on the earthworms. Digestate therefore provides a suitable fertiliser for organic farming. This suitability could be improved by drying or separation to increase the OM content making its properties closer to those of slurry whilst still retaining the higher content of plant available nitrogen.

Seasonally loaded waste stabilisation ponds: a novel application for intermittent discharge.

This research examined the use of a single facultative pond for treatment of an intermittent discharge from a UK campsite. The system was monitored over an 11-month period to determine the optimum time for discharge in terms of quality standards. The results showed that based on organic strength, discharge was possible in winter between November and March but February was the optimum to meet nutrient and suspended solids requirements. The pond showed rapid acclimatisation to the influent wastewater, with biochemical oxygen demand removal rates during the filling period of around 60 kg ha(-1) day(-1) and removal efficiencies of ∼95% after maturation. The system proved simple to operate. A major design factor is the requirement for storage of net incoming precipitation, which may provide dilution of residual pollutants but requires additional system capacity.

Calibration of a simple model for waste stabilisation pond performance in seasonal climates.

The paper describes the calibration of a model for waste stabilisation pond (WSP) performance in seasonal climates, based on the use of readily available climate data sets. Calibration data were taken from a wide geographical area of Canada and the USA, including coastal and moderately seasonal sites. Good agreement with measured values was shown using a biochemical oxygen demand (BOD) decay constant of 0.3 day(-1) for facultative ponds and 0.07-0.1 day(-1) for storage/maturation ponds with a temperature-related Arrhenius constant of 1.05, and a fixed BOD decay constant of 0.007 day(-1) at water temperatures below 0 °C. The results suggested that such models could potentially be used as the basis for WSP design guidelines tailored to a wide range of climatic conditions.

Reducing the environmental impact of methane emissions from dairy farms by anaerobic digestion of cattle waste.

Four dairy cattle farms considered representative of Northern Spain milk production were studied. Cattle waste was characterised and energy consumption in the farms was inventoried. Methane emissions due to slurry/manure management and fuel consumption on the farms were calculated. The possibility of applying anaerobic digestion to the slurry to minimise emissions and of using the biogas produced to replace fossil fuels on the farm was considered. Methane emissions due to slurry management (storage and use as fertiliser) ranged from 34 to 66kg CH(4)cow(-1)year(-1) for dairy cows and from 13 to 25kg CH(4)cow(-1)year(-1) for suckler calves. Cattle on these farms are housed for most of the year, and the contribution from emissions from manure dropped in pastures is insignificant due to the very low methane conversion factors. If anaerobic digestion were implemented on the farms, the potential GHG emissions savings per livestock unit would range from 978 to 1776kg CO(2)eq year(-1), with the main savings due to avoided methane emissions during slurry management. The methane produced would be sufficient to supply digester heating needs (35-55% of the total methane produced) and on-farm fuel energy requirements.

Regulation of ovine and porcine stearoyl coenzyme A desaturase gene promoters by fatty acids and sterols.

Stearoyl CoA desaturase (SCD) is responsible for converting SFA into MUFA and plays an important role in regulating the fatty acid composition of tissues. Although the number of SCD isoforms differs among species, SCD-1 is the predominant isoform expressed in the major lipogenic tissues of all species studied. The SCD-1 gene promoter region has been cloned for several species, including the human, mouse, pig, and recently, the cow. In this study, we cloned and partially characterized the ovine SCD promoter region. Sequence alignment showed a high degree of similarity with published bovine (94%) and porcine (92%) sequences. This included a highly conserved PUFA response region, which was also similar to that found in the human SCD and mouse SCD-1 promoters. Previous studies have indicated that there may be species differences in the regulation of SCD promoter activity by fatty acids. Using promoter-reporter gene (luciferase) constructs transfected into both HEK 293 and McA-RH7777 cells (kidney- and liver-derived cell lines, respectively), we showed the activity of the SCD promoter from 4 different species (mouse, human, pig, and sheep) to be reduced in a dose-dependent manner by addition of unsaturated fatty acids to the media, with linoleic acid being more potent than oleic acid after a 24-h treatment at 60 microM. This effect was dependent on the presence of the PUFA response region. In each of the species studied, the PUFA response region of the SCD promoter was shown to have an active sterol response element, which responded to treatment of cells with sterol or overexpression of the truncated active form of sterol regulatory element binding protein-1c. Thus, any species differences in previously reported regulation of SCD expression by fatty acids are not due to differences in promoter structure between species, but are more likely to depend on the cell type being studied or the relative concentrations and distribution of sterol regulatory element binding proteins or other transcription factors.

Regulation of hepatic gene expression by saturated fatty acids.

Diets rich in saturated fatty acids have long been associated with increased plasma cholesterol concentrations and hence increased risk of cardiovascular disease. More recently, they have also been suggested to promote the development of non-alcoholic fatty liver disease. While there is now considerable evidence to suggest that polyunsaturated fatty acids exert many of their effects through regulating the activity of transcription factors, including peroxisome proliferator activated receptors, sterol regulatory binding proteins (SREBPs) and liver X receptor, our understanding of how saturated fatty acids act is still limited. Here we review the potential mechanisms whereby saturated fatty acids modulate hepatic lipid metabolism thereby impacting on the synthesis, storage and secretion of lipids. Evidence is presented that their effects are, at least partly, mediated through modulation of the activity of the SREBP family of transcription factors.

Dietary omega-3 and -6 polyunsaturated fatty acids affect the composition and development of sheep granulosa cells, oocytes and embryos.

The evidence that omega-3 (n-3) and -6 (n-6) polyunsaturated fatty acids (PUFAs) have differential effects on ovarian function, oocytes and embryo quality is inconsistent. We report on the effects of n-3 versus n-6 PUFA-enriched diets fed to 36 ewes over a 6-week period, prior to ovarian stimulation and follicular aspiration, on ovarian steroidogenic parameters and embryo quality. Follicle number and size were unaltered by diet, but follicular-fluid progesterone concentrations were greater in n-3 PUFA-fed ewes than in n-6 PUFA-fed ewes. The percentage of saturated FAs (mostly stearic acid) was greater in oocytes than in either granulosa cells or plasma, indicating selective uptake and/or de novo synthesis of saturated FAs at the expense of PUFAs by oocytes. High-density lipoproteins (HDLs) fractionated from sera of these ewes increased granulosa cell proliferation and steroidogenesis relative to the FA-free BSA control during culture, but there was no differential effect of n-3 and n-6 PUFAs on either oestradiol or progesterone production. HDL was ineffective in delivering FAs to embryos during culture, although n-6 PUFA HDL reduced embryo development. All blastocysts, irrespective of the treatment, contained high levels of unsaturated FAs, in particular linoleic acid. Transcripts for HDL and low-density lipoprotein (LDL) receptors (SCARB1 and LDLR) and stearoyl-CoA desaturase (SCD) are reported in sheep embryos. HDL reduced the expression of transcripts for LDLR and SCD relative to the BSA control. The data support a differential effect of n-3 and n-6 PUFAs on ovarian steroidogenesis and pre-implantation development, the latter in the absence of a net uptake of FAs.

Extraction and quantitative analysis of stearoyl-coenzyme A desaturase mRNA from dairy cow milk somatic cells.

Study of stearoyl-coenzyme A desaturase (SCD) gene expression in the bovine mammary gland is limited by restricted availability of mammary tissue samples from biopsy or postmortem sampling of cows during temporal experiments. A technique was developed to isolate total RNA from somatic cells in bovine milk and to analyze SCD mRNA expression by quantitative reverse-transcription PCR. Total RNA yield was lower than in a previous goat study and was related to numbers of viable somatic cells. To obtain sufficient total RNA, 1-L milk samples were taken and stored for up to 24 h at 4 degrees C. Complementary DNA prepared from somatic cells showed a 99% match with the published sequence for SCD mRNA in bovine adipose tissue. Stearoyl-CoA desaturase mRNA abundance relative to beta-actin mRNA for 12 cows sampled across 4 time points varied (mean +/- SE) from 0.88 +/- 0.17 to 4.40 +/- 0.50. Fifty-five percent of variation was due to individual cows and 42% was due to daily variation within cows. Relative abundance of SCD mRNA was not related to the number of viable somatic cells or total RNA extracted from samples, but it was related to mammary desaturase activity, as indicated by changes in milk C14 fatty acid concentrations. We concluded that somatic cells provide a noninvasive and repeatable alternative to mammary tissue samples obtained by biopsy or postmortem.

Potential of anaerobic digestion for mitigation of greenhouse gas emissions and production of renewable energy from agriculture: barriers and incentives to widespread adoption in Europe.

The paper considers the role of anaerobic digestion in promoting good agricultural practice on farms and the contribution this would make to reducing the environmental impacts associated with manure management. There are no regulatory drivers to promote the use of digestion in Europe, and the technology has only been widely adopted where economic drivers and coherent policies have been implemented at a national level. These measures have included direct subsidy on the energy price paid for "green electricity", and exemption of tax when biogas is used as a vehicle fuel. In those countries where financial incentives are not available or where a financial penalty is incurred through the regulatory regime, the uptake of digestion has been poor. Even with subsidies, digestion of animal manures as a single substrate is not common, and countries with successful schemes have achieved this either by permitting the import of wastes onto the farm or offering bonus subsidies for the use of energy crops. Both of these measures improve the energy efficiency of the process by increasing the volumetric methane production, although concerns are expressed that attention could concentrate on energy production at the expense of improving manure management.

Influence of annual climate variability on design and operation of waste stabilisation ponds for continental climates.

WSPs are widely used in North America, and offer huge potential for other continental climate regions. The standard design and operating protocol is robust even at high latitudes, but may be conservative elsewhere. A simple model based on first-order kinetics for biochemical oxygen demand (BOD) is used to consider some alternative design and operating protocols, using long-term daily climate records for cities across continental central Asia. Options include changing the discharge period; retaining treated water in the pond over the winter; and changing the facultative pond loading. Annual variability in climate parameters has a major effect, in particular on the date at which treated wastewater meets appropriate standards for discharge or re-use: the earlier the discharge, the greater the variability in effluent quality. Skilful management of these systems may therefore be required to maximise their performance. While current models require development, it is clear modelling could provide tools and guidelines that would allow the design of continental climate WSP to be tailored to specific regional and local climate conditions.

Regulation of gene transcription by fatty acids.

Dietary fat is well recognised as an important macronutrient that has major effects on growth, development and health of all animals including humans. The amount and type of fat in the diet impacts on many aspects of metabolism including lipoprotein pathways, lipid synthesis and oxidation, adipocyte differentiation and cholesterol metabolism. It has become increasingly apparent that many of these effects may be due to direct modulation of expression of key genes through the interaction of fatty acids with certain transcription factors. Peroxisome proliferator-activated receptors (PPARs), the liver X receptors (LXRs), hepatic nuclear factor 4 (HNF-4) and sterol regulatory binding proteins (SREBPs) represent four such factors. This review focuses on emerging evidence that the activity of these transcription factors are regulated by fatty acids and the interactions between them may be responsible for many of the effects of fatty acids on metabolism and the development of chronic disease.

Effect of feeding rumen-protected conjugated linoleic acid on carcass characteristics and fatty acid composition of sheep tissues.

Two experiments were conducted to determine the effectiveness of a rumen-protected CLA (pCLA) supplement and the impact of feeding this pCLA on carcass characteristics and tissue fatty acid composition of lambs. In Exp. 1, a CLA-80 preparation (80% pure CLA; contained similar proportions of cis-9, trans-11, and trans-10, cis-12 CLA), protected against rumen degradation, was fed to sheep, and the proportion of CLA reaching the duodenum was determined. A 3 x 3 Latin square design was used with 3 diets (1.4 kg of concentrate-based control diet, the same control diet plus 22 g of CLA-80, or the same control diet plus 110 g of pCLA/d), 3 feeding periods, and 3 rumen and duodenally cannulated sheep (Mule x Charolais males, 10 mo of age, BW 55.3 +/- 1.8 kg). After 7 d of feeding, sheep were ruminally infused with chromium EDTA and Yb acetate for 7 d, after which samples of duodenal digesta were collected every 6 h for 48 h to determine the quantity of CLA reaching the small intestine each day. The amounts of CLA cis-9, trans-11 and trans-10, cis-12, and combined isomers, flowing through the duodenum each day were greater (P = 0.01) in sheep fed pCLA. Approximately 65% of the pCLA avoided rumen biohydrogenation, with the ratio of the 2 main isomers remaining similar. In Exp. 2, 36 Mule x Charolais ewe lambs (approximately 13-wk old, average initial BW 29.3 kg) were fed 3 levels of the pCLA or Megalac, which were fed to provide an equivalent energy content at each pCLA level. Lambs were randomly assigned to 1 of 7 treatment groups, which were fed for 10 wk to achieve a growth rate of 180 g/d. Treatments included the basal diet and the basal diet plus 25, 50, or 100 g of pCLA/kg of diet or the equivalent amount of Megalac. In liver (P < 0.001) and all adipose tissue depots studied, the proportions of both CLA isomers increased (P = 0.02) with the amount of pCLA fed but were not altered with increasing of Megalac. Although there was no effect of treatment on cis-9, trans-11 CLA content, accumulation (P < 0.001) in the LM with increasing of pCLA supplementation was observed for the trans-10, cis-12 isomer. Although tissues had been enriched with CLA, there was no evidence of a reduction in adipose tissue or an increase in muscle mass in these sheep. However, an effect of pCLA on tissue fatty acid composition was consistent with an inhibition of stearoyl-CoA desaturase.

Differing effects of forage and concentrate diets on the oleic acid and conjugated linoleic acid content of sheep tissues: the role of stearoyl-CoA desaturase.

Feeding sheep concentrate-based diets increases the oleic acid content of their tissues, whereas the cis-9, trans-11 conjugated linoleic acid (CLA) content is increased by feeding forage diets. Both these metabolic transformations could be attributable to increased activity of stearoyl-CoA desaturase (SCD). Therefore, the effect of forage or concentrate feeding regimens on the fatty acid composition of sheep tissues were investigated to determine whether any changes are related to an alteration of SCD mRNA levels. Twenty-four ewe lambs were randomly allotted to one of three dietary treatment groups: 1) dehydrated grass pellets, 2) concentrate diet fed to achieve a growth rate similar to that of the dehydrated grass pellets, and 3) the same concentrate diet approaching ad libitum intake. As expected, animals fed ad libitum concentrates grew at a greater (P = 0.001) rate (280 g/d) than those fed either of the other two diets (180 g/d), which were similar. In samples of liver and the three adipose tissue depots studied, the concentration of oleic acid from sheep fed either level of the concentrate diet was greater (P < 0.001) than from animals fed forage. This was associated with an increase (P < 0.05) in the ratio of SCD to acetyl-CoA carboxylase mRNA in adipose tissue and liver. Compared with concentrate-fed, the forage-fed lambs had increased (P < 0.05) levels of the cis-9, trans-11 isomer of CLA and C18:1, trans-11 in all their tissues, although the levels of SCD mRNA were lower. It therefore seems that the increased oleic acid content of sheep tissues in response to concentrate-rich diets is associated with an increase in SCD gene expression. By contrast, the increased concentration of CLA in animals fed forage-based diets is associated with an increase in substrate (C18:1 trans-11) availability.

Insulin and dexamethasone regulate stearoyl-CoA desaturase mRNA levels and fatty acid synthesis in ovine adipose tissue explants.

Sheep adipose tissue explants were maintained in culture for 24 h in the presence of insulin, dexamethasone, or insulin and dexamethasone, and stearoyl-CoA desaturase (SCD) messenger RNA (mRNA) levels and fatty acid synthesis were measured. Insulin increased SCD mRNA levels (P = 0.008) and synthesis of both saturated (P = 0.07) and unsaturated (P < 0.001) fatty acids but had the greatest effect on unsaturated fatty acid synthesis, resulting in the overall production of a greater (P < 0.001) proportion of monounsaturated fat. Dexamethasone, alone, had the opposite effect but actually potentiated the effect of insulin in stimulating SCD expression and both saturated and monounsaturated fatty acid synthesis, without affecting the relative proportions of each. Across adipose tissue depots, the effect of hormones was similar, although the increase in SCD mRNA levels (P = 0.008) and monounsaturated fatty acid synthesis (P < 0.001) was greater in subcutaneous adipose tissue than in the internal (omental and perirenal) depots. These data clearly show that, in ovine adipose tissue, changes in SCD gene expression in response to insulin and dexamethasone are associated with changes in monounsaturated fatty acid synthesis and suggest that it may be possible to develop strategies to manipulate sheep tissues to produce a less-saturated fatty acid profile.

A role for smooth endoplasmic reticulum membrane cholesterol ester in determining the intracellular location and regulation of sterol-regulatory-element-binding protein-2.

Cellular cholesterol homoeostasis is regulated through proteolysis of the membrane-bound precursor sterol-regulatory-element-binding protein (SREBP) that releases the mature transcription factor form, which regulates gene expression. Our aim was to identify the nature and intracellular site of the putative sterol-regulatory pool which regulates SREBP proteolysis in hamster liver. Cholesterol metabolism was modulated by feeding hamsters control chow, or a cholesterol-enriched diet, or by treatment with simvastatin or with the oral acyl-CoA:cholesterol acyltransferase inhibitor C1-1011 plus cholesterol. The effects of the different treatments on SREBP activation were confirmed by determination of the mRNAs for the low-density lipoprotein receptor and hydroxymethylglutaryl-CoA (HMG-CoA) reductase and by measurement of HMG-CoA reductase activity. The endoplasmic reticulum was isolated from livers and separated into subfractions by centrifugation in self-generating iodixanol gradients. Immunodetectable SREBP-2 accumulated in the smooth endoplasmic reticulum of cholesterol-fed animals. Cholesterol ester levels of the smooth endoplasmic reticulum membrane (but not the cholesterol levels) increased after cholesterol feeding and fell after treatment with simvastatin or C1-1011. The results suggest that an increased cellular cholesterol load causes accumulation of SREBP-2 in the smooth endoplasmic reticulum and, therefore, that membrane cholesterol ester may be one signal allowing exit of the SREBP-2/SREBP-cleavage-regulating protein complex to the Golgi.