Feeding mice in early life a diet containing an experimental infant milk formula (Nuturis®; eIMF), with a lipid structure similar to human milk, transiently lowered body weight (BW) and fat mass gain upon Western-style diet later in life, when compared with mice fed diets based on control IMF (cIMF). We tested the hypothesis that early-life eIMF feeding alters the absorption or the postabsorptive trafficking of dietary lipids in later life. Male C57BL/6JOlaHsd mice were fed eIMF/cIMF from postnatal day 16–42, followed by low- (LFD, American Institute of Nutrition (AIN)-93 G, 7 wt% fat) or high-fat diet (HFD, D12451, 24 wt% fat) until day 63–70. Lipid absorption rate and tissue concentrations were determined after intragastric administration of stable isotope (2H or 13C) labelled lipids in separate groups. Lipid enrichments in plasma and tissues were analysed using GC-MS. The rate of triolein absorption was similar between eIMF and cIMF fed LFD: 3·2 (sd 1·8) and 3·9 (sd 2·1) and HFD: 2·6 (sd 1·7) and 3·8 (sd 3·0) % dose/ml per h. Postabsorptive lipid trafficking, that is, concentrations of absorbed lipids in tissues, was similar in the eIMF and cIMF groups after LFD. Tissue levels of absorbed TAG after HFD feeding were lower in heart (–42 %) and liver (–46 %), and higher in muscle (+81 %, all P < 0·05) in eIMF-fed mice. In conclusion, early-life IMF diet affected postabsorptive trafficking of absorbed lipids after HFD, but not LFD. Changes in postabsorptive lipid trafficking could underlie the observed lower BW and body fat accumulation in later life upon a persistent long-term obesogenic challenge.

Breast-feeding is associated with a lower risk of developing obesity during childhood and adulthood compared with feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®) programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD) compared with a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breast milk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition and a cIMF, on body weight, glucose homoeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised approximately 50 % milk fat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal day (PN) 16–42 followed by an HFD until PN168. Feeding eIMF v. cIMF in early life resulted in a lower body weight (–9 %) and body fat deposition (–14 %) in adulthood (PN105). The effect appeared transient, as from PN126 onwards, after 12 weeks’ HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27 %) epididymal fat depots and a lower (–26 %) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlie the programming effect observed. Prolonged exposure to an HFD challenge partly overrules the programming effect of early diet.

The quality of dietary lipids in the maternal diet can programme the offspring to diseases in later life. We investigated whether the maternal intake of palm oil or interesterified fat, substitutes for trans-unsaturated fatty acids (FA), induces metabolic changes in the adult offspring. During pregnancy and lactation, C57BL/6 female mice received normolipidic diets containing partially hydrogenated vegetable fat rich in trans-unsaturated fatty acids (TG), palm oil (PG), interesterified fat (IG) or soyabean oil (CG). After weaning, male offspring from all groups received the control diet until day 110. Plasma glucose and TAG and liver FA profiles were ascertained. Liver mitochondrial function was accessed with high-resolution respirometry by measuring VO2, fluorimetry for detection of hydrogen peroxide (H2O2) production and mitochondrial Ca2+ uptake. The results showed that the IG offspring presented a 20 % increase in plasma glucose and both the IG and TG offspring presented a 2- and 1·9-fold increase in TAG, respectively, when compared with CG offspring. Liver MUFA and PUFA contents decreased in the TG and IG offspring when compared with CG offspring. Liver MUFA content also decreased in the PG offspring. These modifications in FA composition possibly affected liver mitochondrial function, as respiration was impaired in the TG offspring and H2O2 production was higher in the IG offspring. In addition, mitochondrial Ca2+ retention capacity was reduced by approximately 40 and 55 % in the TG and IG offspring, respectively. In conclusion, maternal consumption of trans-unsaturated and interesterified fat affected offspring health by compromising mitochondrial bioenergetics and lipid metabolism in the liver.

Epidemiological studies have demonstrated protective effects of breast-feeding on childhood obesity. Differences between human milk and infant milk formula (IMF) in dietary lipid structure may contribute to this effect. In our mouse model, feeding a diet containing large lipid droplets coated with phospholipids (PL) (Nuturis®; PL of milk fat globule membrane (MFGM) fraction origin) in early life protected against excessive body fat accumulation following a diet challenge in adult life. We now set out to determine the relevance of increased droplet size and/or MFGM lipid droplet coating to the observed anti-obesogenic effects in adult life. From day 16 to 42, male mouse pups were exposed to diets with small (S) or large (L) lipid droplets (0·3 v. 2·9 µm average mode diameter, respectively), either without MFGM or with MFGM coating around the lipid droplet, resulting in four groups: S (control diet), L, Scoating and Lcoating (Nuturis® IMF diet). Mice were subsequently challenged with a Western-style diet until dissection at postnatal day 98. A non-challenged group served as reference (REF). We repeatedly determined body composition between postnatal day 42 and 98. At day 98 plasma and gene expression measurements were performed. Only the Nuturis® IMF diet (Lcoating) in early life containing MFGM-coated large lipid droplets reduced body fat mass to a level comparable with the REF group. These data support the notion that the structural aspects of lipids in human milk, for example, both lipid droplet size as well as the MFGM coating, may contribute to its reported protective effect against obesity in later life.

Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: ‘adiponectin’, ‘dietary lipid’, ‘randomized controlled trials (RCT)’). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: − 0·04 (95 % CI − 0·82, 0·74) μg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95 % CI 0·07, 0·47) μg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; − 0·74 (95 % CI − 1·38, − 0·10) μg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.

Obese individuals have more (hyperplastic) and larger (hypertrophic) adipocytes in their white adipose tissue (WAT) than normal-weight individuals. The difference in cell number emerges early in childhood, suggesting that this is a critical period for being susceptible to obesity. Breast-feeding has been shown to be protective against obesity, and we have previously shown in mice that the physical structure of lipids in human milk may contribute to this protective effect. In the present study, we investigated how differences in the physical structure of lipids in the early diet may modulate adipose tissue development. Male mice were fed a diet containing control infant milk formula (Control IMF; Danone Research) or Nuturis® (Concept IMF with large phospholipid-coated lipid droplets; Danone Research) from postnatal day (PN)16 to 42. Subsequently, mice were challenged with a moderate Western-style diet (WSD) until PN98, and body composition was monitored by dual-energy X-ray absorptiometry. Epididymal WAT was analysed for adipocyte size, number and gene expression of metabolic transcription factors. Early Concept IMF exposure reduced fat accumulation during the WSD challenge by 30 % compared with the Control IMF. It reduced adipocyte size without affecting adipocyte number in adult mice. The Concept IMF decreased the expression of PPARγ, CCAAT/enhancer-binding protein and retinoid X receptor α in WAT in adulthood, key regulators of metabolic activity. In conclusion, Concept IMF exposure in early life reduced susceptibility to obesity in adult life, by preventing adipocyte hypertrophia upon adult dietary challenge without affecting adipogenesis. These data emphasise the importance of the physical properties of dietary lipids in early life in obesity risk later in life.

Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (n = 16 per group) derived from either: (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5 g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar. Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating the effect of dietary lipids on vascular function. The workshop highlighted the need for intervention studies to be sufficiently powered for these measures and that they should be corroborated with other, more validated, risk factors for CVD. Work presented at the workshop suggested a beneficial effect of long-chain n-3 PUFA and a detrimental effect of trans fatty acids. The workshop also considered the importance of the choice of study population in dietary intervention studies and that ‘at risk’ subgroups within the general population may be more appropriate than subjects that are unrepresentatively healthy.

In the present study, we compared the effects of nibbling and gorging on postprandial lipaemia and lipoproteins, hepatic lipid uptake and atheroma deposition. New Zealand White rabbits were fed on a low-fat (LF) control diet or a peanut oil- (10 g/d) and cholesterol- (0·5 g/d) enriched (HF) diet with the fat and cholesterol components given either by nibbling (HF-N) or gorging (HF-G). After 4 and 8 weeks, rabbits were given a test meal, which was either nibbled or taken as a bolus. The LF diet did not noticeably alter postprantial lipid variables. Triacylglycerol levels, 0–35 h lipid responses and plasma accumulation of dietary lipids were significantly higher in the HF-G group than in the HF-N group, despite higher post-heparin plasma lipase activities. Furthermore, as studied on cultured isolated hepatocytes, the higher the rate of supply of triacylglycerol- and cholesterol-rich lipoproteins (TCRL), the lower the rate of lipid uptake and bile salt secretion. Atheroma deposition was significantly increased by gorging the HF diet and was correlated with levels of most postprandial lipid variables. We conclude that gorging v. nibbling a fat and cholesterol-enriched diet exacerbates postprandial lipaemia by reducing the rate of TCRL clearance and favours atheroma deposition.

The effect of a dietary supplement of calcium soaps of fatty acids on luteal steroidogenic activity was studied in sheep. Mature 3- to 5-year-old North Country Cheviot ewes were given either a pelleted control diet (C; grass, beet pulp, barley; no. = 15) providing daily, 29⋅8 g nitrogen and 13⋅7 MJ of metabolizable energy (ME) or the same diet with 5% (w/w) of the ingredients replaced with protected lipid (C + CaFA; calcium soaps of fatty acids, Megalac, Volac Etd; no. = 15) for 21 days. The latter diet provided daily 30⋅2 g nitrogen and 15⋅9 MJ ME. At the end of the feeding period the ewes were slaughtered and blood samples and ovaries were collected from individual animals. The numbers of large- (≤ 4 mm diameter) and small- to medium-sized (1 to 3 mm diameter) follicles were recorded and follicular fluids from both size groups were stored for later analyses following centrifugation. Each mature corpus luteum (CL) was isolated from its ovary and sliced to provide a pair of ca. 0⋅3 mm diameter sections. These sections (mean = 163 (s.e.12) mg) were cultured separately (4 h; 39°C; 5% CO2) in 3 ml Medium 199 in the absence or presence of 100 μIU LH. Dietary supplementation of calcium soaps of fatty acids increased progesterone concentrations in the plasma (P < 0⋅05) and follicular fluid (P < 0⋅01 and P < 0⋅05 for large and small to medium follicles, respectively); trigylcerides in plasma (P < 0⋅05); total cholesterol in plasma (P < 0⋅001) and follicular fluid (P < 0⋅001); HDL-cholesterol in plasma (P < 0⋅001) and follicular fluid (P < 0⋅01) and LDL-cholesterol in plasma (P < 0⋅01). Progesterone released by luteal tissue into the culture medium in vitro from ewes given protected lipid was higher than that from tissue of control ewes (P < 0⋅05) and supplementary LH in vitro stimulated progesterone secretion by luteal tissues from both groups (P < 0⋅05). In conclusion, a dietary supplement of calcium soaps of fatty acids altered the intra-follicular environment surrounding the oocyte and follicular cells and enhanced luteal function in sheep.

The aim of the present study was to evaluate the links between chronic fat-cholesterol intake, postprandial lipaemia and atherogenesis in New Zealand White rabbits. Adult rabbits were fed on either a low-fat control diet (LF) or a high-fat, high-cholesterol diet (HF). Rabbits received a test meal containing [3H]cholesterol and [14C]triolein on days 0 and 63 for the LF group and days 14,28, 42,63 and 84 for the HF group. Blood was collected 24h post-absorptively and 10,24,34 and 48h after test-meal intake. Post-absorptive as well as postprandial lipoproteins and lipaemia were not modified in the LF rabbits, who did not show any atheroma deposition on day 119. In HF rabbits, postprandial plasma triacylglycerols peaked 24–34h after meal intake. The 0-48 h areas under the curves of triacylglycerol andtriacylglycerol-rich lipoproteins (TRL) steadily increased with time of chronic lipid feeding with values significantly higher than those in the LF rabbits. The postprandial plasma and TRL concentrations of dietary radiolabelled lipids were significantly higher in HF than LF rabbits. Post-heparin lipoprotein lipase (EC 3.1.1.34) and hepatic lipase (EC 3.1.1.3) activities were twofold higher in HF rabbits than in LF rabbits at day 105. In HF rabbits, a marked atheroma plaque deposition in the aorta was observed (30·9 (SE 3·9) % of total surface). The extent of atheroma deposition was positively correlated to the postprandial responses of plasma total triacylglycerols and dietary-derived lipids as well as total cholesterol and dietary-derived cholesterolin HF rabbits. In conclusion, chronic ingestion of a HF diet led to marked increases in postprandial lipaemia and TRL particles, and atheroma deposition.

To obtain further information about the immunomodulatory effects of specific dietary fatty acids, weanling male rats were fed for 6 weeks on high-fat (178 g/kg) diets which differed according to the principal fatty acids present. The nine diets used differed in their contents of palmitic, oleic, linoleic and α-linolenic acids; as a result the total polyunsaturated fatty acid (PUFA) content and the PUFA: saturated fatty acid ratio varied (from 17·8 to 58·5 g/lW g fatty acids and from 0·28 to 5·56 respectively). The n−6 PUFA: n−3 PUFA ratio was kept constant in all diets at approximately 7·0.The fatty acid compositions of the serum and of spleen lymphocytes were significantly influenced by that of the diet fed. The ex vivo proliferation of spleen lymphocytes decreased as the levelof oleic acid in the diet increased. Spleen natural killer cell activity decreased as the oleic acid content of the diet increased and increased as the palmitic acid content of the diet increased. The extent of the effects of these fatty acids on lymphocyte functions was modified by the nature of the background fatty acid composition of the diet.

The influence of dietary lipids on the liver microsomal mixed function oxidase system and on pentobarbital-induced sleeping time was studied in rats. Giving diets containing (g/kg) 150 olive oil, 150 lard or 150 soya-bean oil for 21 d (Expt 1) increased the cytochrome P-450 content in the order: olive oil < lard < soya-bean oil. When diets containing (g/kg) 150 lard, 150 soya-bean oil, 150 sardine oil or an equal mixture of 50 of each oil were given for 15 d (Expt 2), the cytochrome P-450 content and aminopyrine N-demethylase activity were significantly higher in the sardine-oil and mixed-oil groups than in the lard group, and the activity of aminopyrine N-demethylase was also significantly higher in the soya-bean oil group compared with the lard group. A significantly higher activity of NADPH-cytochrome c reductase (EC 1.6.2.5) was observed in the sardine-oil group than in the other three groups. Aniline hydroxylase activity and cytochrome b5 content remained unchanged in all the groups. Pentobarbital-induced sleeping time measured on day 15 (Expt 2) varied inversely with the changes in cytochrome P-450 content and aminopyrine N-demethylase activity in the three single-fat groups, but not in the mixed-oil group, reflecting liver microsomal metabolic activity for pentobarbital in vivo. From these results, it appears that high intakes of polyunsaturated fatty acids (18:2n-6, 18:3n-3, 20:5n-3 and 22:6n-3) stimulate the liver microsomal mixed function oxidase system.