Alastair MacGibbon

Modulation of Osteoclastogenesis by Fatty Acids

Clinical studies have shown that total body fat mass is related to both bone density and fracture risk and that fat ingestion reduces bone turnover. These effects are at least partially mediated by endocrine mechanisms, but it is possible that lipids might act directly on bone. We assessed the effects of broad fractions of milk lipids in osteoblasts, bone marrow, and neonatal mouse calvariae. Several milk fractions and their hydrolysates inhibited osteoclastogenesis in bone marrow cultures, so we assessed the effects of free fatty acids in this model. Saturated fatty acids (0.1-10 microg/ml) inhibited osteoclastogenesis in bone marrow cultures and RAW264.7 cells. This effect was maximal for C14:0 to C18:0 fatty acids. The introduction of greater than 1 double bond abrogated this effect; omega3 and omega6 fatty acids had comparable low activity. Osteoblast proliferation was modestly increased by the antiosteoclastogenic compounds, ruling out a nonspecific toxic effect. Active fatty acids did not consistently change expression of receptor activator of nuclear factor-kappaB ligand or osteoprotegerin in osteoblastic cells nor did they affect the activity of key enzymes in the mevalonate pathway. However, receptors known to bind fatty acids were found to be expressed in osteoblastic (GPR120) and osteoclastic (GPR40, 41, 43, 120) cells. A synthetic GPR 40/120 agonist mimicked the inhibitory effects of fatty acids on osteoclastogenesis. These findings provide a novel link between lipid and bone metabolism, which might contribute to the positive relationship between adiposity and bone density as well as provide novel targets for pharmaceutical and nutriceutical development.

Some recent advances in the basic chemistry of milk proteins and lipids

Abstract Sophisticated analytical tools and techniques now are being applied to the study of the major components of milk (protein, fat, lactose and mineral interaction products). Through steady improvement, such tools have moved from the stage of exciting academic breakthroughs to become reliable work-horses. Examples are the application of genetic engineering to study the stability of β-lactoglobulin, GLC-MS to examine the composition of the fat fraction, NMR techniques to study the solution structures of casein peptides, or α-lactalbumin and X-ray crystallography to examine whey protein structure. The future challenge will be to gain understanding of mixed and modified systems involving two or more phases with a combination of dairy and non-dairy ingredients.

Lipid-lowering effects of a modified butter-fat: a controlled intervention trial in healthy men

Objective: To investigate the lipid-lowering potential of a butter-fat modified through manipulations in bovine feeding to increase the unsaturated:saturated fatty acid ratio.Design: Double-blind, randomised, cross-over intervention trial.Setting: University of Auckland Human Nutrition Unit, New Zealand.Subjects: Twenty healthy, male subjects.Intervention: A residential trial in which all foods and beverages were provided during two intervention periods, comprising 3 weeks of high unsaturated ‘modified’ vs 3 weeks of saturated ‘control’ butter feeding separated by a 4 week washout. Diets were of typical composition of 39 percentage energy (en%) fat (20 en% butter-fat), 48 en% CHO, 13 en% protein.Results: There was a significant decrease in both total (P<0.05, −7.9%) and LDL-cholesterol (P<0.01, −9.5%) during modified butter feeding. There was no significant effect of treatment on a range of other risk factors including HDL-cholesterol, triglyceride, apolipoprotein A or B, nonesterified fatty acids (NEFA), haemostatic clotting factor VII and fibrinogen or glucose (P>0.05). Subjects were maintained in energy balance and there was no significant change in body weight during intervention. Butter-fat composition alone differed between treatments.Conclusions: A significant improvement in cardiovascular risk can be achieved by moderate changes in dietary fatty acid profile, achieved through a common and well accepted food source, butter-fat.Sponsorship: New Zealand Dairy Board, Wellington; Auckland Uniservices Ltd, Auckland; Maurice & Phyllis Paykel Trust, Auckland, New Zealand.

Effects of skim milk powder enriched with glycomacropeptide and G600 milk fat extract on frequency of gout flares: a proof-of-concept randomised controlled trial

Objectives Previous laboratory studies have identified two dairy fractions, glycomacropeptide (GMP) and G600 milk fat extract (G600), with anti-inflammatory effects in models of acute gout. The aim of this proof-of-concept clinical trial was to test the hypothesis that daily intake of skim milk powder (SMP) enriched with GMP and G600 can prevent gout flares. Methods This was a 3-month randomised double-blind controlled trial of milk products for prevention of gout flares. One hundred and twenty patients with recurrent gout flares were randomised to one of three arms: lactose powder control, SMP control and SMP enriched with GMP and G600 (SMP/GMP/G600). The primary end point was change in the frequency of gout flares using a daily flare diary measured monthly for 3 months. Results The frequency of gout flares reduced in all three groups over the 3-month study period compared with baseline. Over the 3-month study period there was a significantly greater reduction in gout flares in the SMP/GMP/G600 group (analysis of covariance pgroup=0.031, Tukey post hoc test compared with lactose control, p=0.044). Following treatment with SMP/GMP/G600 over the 3-month period, greater improvements were also observed in pain and fractional excretion of uric acid, with trends to greater improvement in tender joint count. Similar adverse event rates and discontinuation rates were observed between the three groups. Conclusions This is the first reported controlled trial of dietary intervention in patients with gout, and suggests that SMP enriched with GMP and G600 may reduce the frequency of gout flares.

Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice

Background It has been argued that a reduction in the Western diet of anti‐inflammatory unsaturated lipids, such as n‐3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases.

Fatty acid chain length, postprandial satiety and food intake in lean men.

High-fat diets are associated with obesity, and the weak satiety response elicited in response to dietary lipids is likely to play a role. Preliminary evidence from studies of medium (MCT) and long chain triglycerides (LCT) supports greater appetite suppression on high-MCT diets, possibly a consequence of direct portal access, more rapid oxidation and muted lipaemia. No data is as yet available on high-SCT diets which also have direct hepatic access. In this study SCT- (dairy fats), MCT- (coconut oil) and LCT-enriched (beef tallow) test breakfasts (3.3 MJ) containing 52 g lipid (58 en% fat) were investigated in a randomized, cross-over study in 18 lean men. All participants were required to complete the 3 study days in randomised order. Participants rated appetite sensations using visual analogue scales (VAS), and energy intake (EI) was measured by covert weighing of an ad libitum lunch meal 3.5 h postprandially. Blood samples were collected by venous cannulation. There were no detectable differences between breakfasts in perceived pleasantness, visual appearance, smell, taste, aftertaste and palatability (P>0.05). There was no significant effect of fatty acid chain length on ratings of hunger, fullness, satisfaction or current thoughts of food, nor did energy (mean, sem: SCT: 4406, 366 kJ; MCT: 4422, 306 kJ; LCT: 4490, 324 kJ; P>0.05) or macronutrient intake at lunch differ between diets. The maximum difference in EI between diets was less than 2%. Postprandial lipaemia also did not differ significantly. We conclude that there was no evidence that fatty acid chain length has an effect on measures of appetite and food intake when assessed following a single high-fat test meal in lean participants.

No evidence of differential effects of SFA, MUFA or PUFA on post-ingestive satiety and energy intake: a randomised trial of fatty acid saturation

BackgroundHigh fat diets have long been associated with weight gain and obesity, and the weak satiety response elicited in response to dietary lipids is likely to play a role. Suppression of appetite and food intake has consistently been shown to be diminished with high fat relative to either high protein or carbohydrate meals. There is however some evidence that the satiating capacity of lipids may be modulated when physicochemical properties are altered, but studies investigating the effect of lipid saturation on appetite have generated inconsistent findings. This study investigated the effects of changes in fatty acid saturation on post-ingestive satiety and energy intake.MethodsHigh-fat (HF) test breakfasts (2.0 MJ) containing 26 g lipid were given to 18 healthy, lean men in a 3 treatment randomised cross-over design, each treatment separated by a washout of at least 3 days. The breakfasts were high in saturated (SFA, 65% of total fat), polyunsaturated (PUFA, 76%) or monounsaturated (MUFA, 76%) fatty acids, and comprised 2 savoury muffins. Participants rated appetite sensations using visual analogue scales (VAS) to assess palatability immediately following the meals, and hunger and fullness prior to the HF breakfast and throughout the day. Energy intake was measured by covert weighing of a lunch meal which was served 3.5 h after the breakfast, and from which the participants ate ad libitum.ResultsThere was no difference in VAS ratings of pleasantness, visual appearance, smell, taste, aftertaste and overall palatability between the 3 high-fat test breakfasts. However, there was also no differential effect of the 3 treatments on ratings of hunger, fullness, satisfaction or prospective food consumption during the 3.5 h following the breakfast meal and over the full 6 h experiment. Energy and macronutrient intake at lunch also did not differ between treatments (mean, sem; SFA: 5275.9 ± 286.5 kJ; PUFA: 5227.7 ± 403.9 kJ; MUFA: 5215.6 ± 329.5 kJ; P > 0.05). The maximum difference in energy intake between treatments was less than 2%.ConclusionsThere was no evidence of a difference in post-ingestion satiety between high fat meals which differed in saturation profile in this group of lean, healthy men.Trial RegistrationACTRN12610000193077

Identification of dairy fractions with anti-inflammatory properties in models of acute gout

Aims Large epidemiological studies have shown that low-fat dairy intake reduces the risk of developing gout. It was hypothesised that factors within dairy fractions inhibit the inflammatory response to monosodium urate monohydrate (MSU) crystals. Methods Dairy fractions were tested in MSU crystal-stimulated THP-1 cell assays. Fractions with inhibitory effects were then tested in the murine urate peritonitis model. Results Two dairy fractions were found to have consistent inhibitory effects. Glycomacropeptide (GMP) and G600 milk fat extract both inhibited interleukin-1β (IL1β) gene and protein expression in the THP-1 cell assay. Conversely, standard milk fat increased IL8 protein expression in the THP-1 cell assay. Oral administration of GMP and G600 milk fat extract inhibited cellular influx in the urate peritonitis model. Conclusions Both protein and lipid fractions within dairy products are capable of modulating the inflammatory response to MSU crystals.

Proximate composition, energy content, and fatty acid composition of marine species from Campbell Plateau, New Zealand

Abstract Campbell Plateau is an important fishing ground for the main commercial New Zealand species. Yet, studies on trophic interactions between species and their nutritional values are limited. The objectives of this study were to determine the proximate composition and energy contents of selected commercial and non‐commercial marine species from Campbell Plateau and their fatty acid (FA) composition, and to evaluate the degree to which species can be differentiated by their FA compositions. We analysed 43 fish specimens from 5 different species (Macruronus novaezelandiae, Lepidorhynchus denticulatus, Pseudophycis backus, Hemerocoetes spp. and Squalus acanthias), 17 cephalopod specimens from 2 species (Nototodarus sloani and Enteroctopus zealandicus), and 6 Metanephrops challengeri (crustacean). The variation of energy contents between fish species was not significant, but their lipid and protein contents varied significantly. FA signatures distinguished the species analysed and, at a broader scale, the type of habitat. Within‐specie s variability was important for benthic species. In general, the diet inference from FA trophic markers was consistent with reported diets from stomach contents.

Age-related memory decline is associated with vascular and microglial degeneration in aged rats

The hippocampus processes memory is an early target of aging-related biological and structural lesions, leading to memory decline. With absent neurodegeneration in the hippocampus, which identified in rodent model of normal aging the pathology underlying age-related memory impairment is not complete. The effective glial-vascular networks are the key for maintaining neuronal functions. The changes of glial cells and cerebral capillaries with age may contribute to memory decline. Thus we examined age associated changes in neurons, glial phenotypes and microvasculature in the hippocampus of aged rats with memory decline. Young adult (6 months) and aged (35 months) male rats (Fisher/Norway-Brown) were used. To evaluate memory, four days of acquisition phase of Morris water maze tasks were carried out in both age groups and followed by a probe trial 2 h after the acquisition. The brains were then collected for analysis using immunochemistry. The aged rats showed a delayed latency (p<0.001) and longer swimming path (p<0.001) to locate a hidden platform. They also spent less time in and made delayed and fewer entries into the correct quadrant during the probe trial. Without seen neuronal degeneration, the aged rats with memory impairments have displayed dopamine depletion, profound vascular and microglial degeneration with reduced vascular endothelial growth factor and elevated GFAP expression in the hippocampus. The data indicate the memory decline with age is associated with neuronal dysfunction, possibly due to impaired glial-vascular-neuronal networks, but not neuronal degeneration. Glial and vascular degeneration found in aged rats may represent early event of aging pathology prior to neuronal degeneration.