The effects of weight loss on FABP4 and RBP4 in obese women with metabolic syndrome.

Fat accumulation is associated with the release of many novel adipokines such as retinol-binding protein 4 and fatty acid-binding protein 4. These adipokines have been linked to insulin resistance, metabolic syndrome, type 2 diabetes and cardiovascular disease. Since weight loss is the first step for the treatment of metabolic syndrome, which increases the risks for both type 2 diabetes and cardiovascular disease, we have investigated the effects of weight loss on serum retinol-binding protein 4 and fatty acid-binding protein 4 in obese individuals with this syndrome. Twenty-nine obese female subjects with metabolic syndrome, aged 18-62 years completed a 2-month weight loss diet plan. Data were collected from dual-energy X-ray absorptiometry and indirect calorimetry. Blood was taken at baseline and at 2 months and assayed for adipokines, lipids, and insulin resistance parameters. The change in circulating fatty acid-binding protein 4 levels were inversely correlated with total weight loss (p<0.02) and lean mass loss (p<0.01), but not with fat mass loss. Retinol-binding protein 4 levels did not track with any measure of body composition. Changes in leptin levels were found to correlate with weight loss (p<0.02), fat loss (p<0.03), and lean mass loss (p<0.05). Fatty acid-binding protein 4 levels increased and retinol-binding protein 4 levels did not change during moderate weight loss in obese women with metabolic syndrome; however, several other risk factors for type 2 diabetes and cardiovascular disease did improve with weight loss.

Differential effects of walnuts vs almonds on improving metabolic and endocrine parameters in PCOS.

BACKGROUND/OBJECTIVES: Polycystic ovary syndrome (PCOS) is commonly associated with insulin resistance, dyslipidemia and increased inflammation, which all benefit from dietary intake of monounsaturated and n-3 polyunsaturated fatty acids (MUFA and n-3 PUFA). Our goal was to compare the effects of MUFA-rich almonds vs n-3/n-6 PUFA-rich walnuts on metabolic and endocrine parameters in PCOS. SUBJECTS/METHODS: Thirty-one PCOS patients randomly received either walnuts or almonds containing 31 g of total fat per day for 6 weeks. At the beginning and at the end, anthropometric parameters, fasting lipids, phospholipid-fatty acids, inflammatory markers, androgens, oral glucose tolerance tests (OGTT) and frequently sampled intravenous-GTT were obtained. RESULTS: Weight remained stable. Within group, walnuts increased the n-3/n-6 essential PUFA in the diet and plasma phospholipids. Walnuts decreased low-density lipoprotein-cholesterol by 6% from 3.76 ± 0.27 to 3.38 ± 0.22 mmol/l (P = 0.05) and apoprotein B by 11% from 0.72 ± 0.04 to 0.64 ± 0.05 g/l (P < 0.03). Although almonds also reduced low-density lipoprotein-cholesterol by 10% and apoprotein B by 9%, these were not significant. Walnuts increased insulin response during OGTT by 26% (P < 0.02). Both walnuts and almonds increased adiponectin (walnuts from 9.5 ± 1.6 to 11.3 ± 1.8 µg per 100 ml, P = 0.0241; almonds from 10.1 ± 1.5 to 12.2 ± 1.4 µg/dl, P = 0.0262). Walnuts decreased HgBA1 from 5.7 ± 0.1 to 5.5 ± 0.1% (P = 0.0006) with significant intergroup difference from almonds (P=0.0470). Walnuts increased sex hormone-binding globulin from 38.3 ± 4.1 to 43.1 ± 4.3 nmol/l (P=0.0038) and almonds reduced free androgen index from 2.6 ± 0.4 to 1.8 ± 0.3 (P = 0.0470). CONCLUSION: Nut intake exerted beneficial effects on plasma lipids and androgens in PCOS.

Effects of variations in live weight gain on bone growth and composition and on markers of bone turnover in lambs.

Growing lambs were fed the same diet at intakes supporting mean live weight gains of 0.1, 0.2 and 0.3 kg day-1, representing slow, intermediate and fast growth groups, respectively. The effects on bone growth and composition, and on blood and urinary bone marker concentrations or excretion rates were monitored. Compared with the slow-growing lambs, the higher intake group grew twice as fast, had higher rates of bone growth (indicated by external metatarsal length), and larger and heavier bones at slaughter. Bones from fast-growing animals had higher collagen and deoxypyridinoline concentrations, and lower Ca:collagen, Ca :P and pyridinoline : deoxypyridinoline ratios, indicating a less mature bone compared with the slow-growing lambs. Bone growth rate had no effect on plasma osteocalcin, bone-specific alkaline phosphatase or growth hormone concentrations, nor on the urinary excretion of pyridinoline and deoxypyridinoline. The results for plasma markers may be explained by an increase in blood volume linked with increased body weight.

Effects of variations in dietary calcium and phosphorus supply on plasma and bone osteocalcin concentrations and bone mineralization in growing pigs.

Growing pigs were fed diets supplying 45% (low), 70% (intermediate) and 100% (high) recommended dietary allowances of calcium (the Ca:P ratio was kept constant), but otherwise adequate in nutrients. The effects of varying calcium and phosphorus intakes on bone and plasma osteocalcin were monitored. Mineral content of the diet did not affect feed conversion and live weight gain. Plasma phosphorus concentrations decreased significantly in pigs fed a low mineral diet compared with those fed the high mineral diet, but there were no changes in plasma calcium and osteocalcin concentrations. Bones from the low mineral group had marked reductions in dry matter, calcium and phosphorus contents, as well as increased collagen, pyridinoline and deoxypyridinoline concentrations: osteocalcin concentrations in bone were unaffected by treatment. The results showed no direct link between osteocalcin and the degree of bone mineralization.

Lipid accumulation in obese Zucker rats is reduced by inclusion of raw kidney bean (Phaseolus vulgaris) in the diet.

The effects of inclusion of different levels of raw kidney bean (Phaseolus vulgaris) of high lectin content (27 g/kg meal) in a high-quality (lactalbumin) control diet were tested in nutritional trials on the growth and metabolism of obese Zucker (fafa) rats and their lean littermates in comparison with pair-fed controls. All diets contained 100 g total protein/kg and either 50 g lipids/kg (low fat) or 150 g lipids/kg (moderate fat). The growth of both obese and lean rats on bean diets was retarded by the daily bean intake in a dose-dependent manner. However, most of this was because bean-fed rats contained less body fat than the controls after 10 d. Thus, after feeding low-fat diets containing up to 130 g kidney bean/kg (lectin intake < or = 0.2 g/kg body weight (BW) per d) in both 10 d and 70 d trials, the bodies of obese rats contained less fat but not protein than their pair-fed controls. Moreover, by increasing the lipid content of the diet to 150 g/kg, the level of bean inclusion could be increased to 280 g/kg (lectin intake > or = 0.4 g/kg BW per d) without loss of body protein and skeletal muscle. Although these rats contained more body fat than those which were fed on low-fat diets, their weight reduction could be accounted for exclusively by reduced lipid content. In contrast, significant body protein loss occurred when the same diet of high lectin content was fed to lean littermates. Plasma insulin levels were significantly depressed in the obese Zucker rats on bean diets but the pancreas was not significantly enlarged nor its insulin content changed in 10 d trials. However, significant pancreatic growth occurred on long-term (70 d) bean feeding compared with pair-fed controls. The results suggest that, in addition to animal nutrition, it may also be possible to use the bean lectin as a dietary adjunct or therapeutic agent to stimulate gut function and ameliorate obesity if a safe and effective dose-range can be established for human subjects.

Effect of diets varying in nitrogen or phosphorus content on indicators of bone growth in lambs.

Growing lambs were fed diets low in nitrogen and phosphorus (LNLP), low in nitrogen and high in phosphorus (LNHP), high in nitrogen and low in phosphorus (HNLP) or high in nitrogen and phosphorus (HNHP) and the effects on bone growth and on blood and urinary bone marker levels or excretion rates were monitored. Plasma calcium concentrations were higher, and phosphorus concentrations lower, in lambs fed the low phosphorus diets but there were no differences in plasma 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) concentrations. Lambs fed both low phosphorus diets (LNLP and HNLP) had lower plasma osteocalcin and higher bone-specific alkaline phosphatase concentrations than those fed the high phosphorus diets. Urinary pyridinoline and deoxypyridinoline excretion were also affected by treatment, with their rates of excretion being highest in lambs fed the diet low in both nitrogen and phosphorus (LNLP). Lambs fed the low phosphorus diets were lighter in weight at slaughter and had lighter bones that were less well mineralized than those fed the high phosphorus diets. Reducing the nitrogen content of the diet appeared to have little effect on bone composition. These results suggest that bone markers that have proved useful in the diagnosis and treatment of bone disease are sensitive to variation in nutrient supply and may prove useful in early detection of nutrient deficiencies that affect bone growth.

Use of sheep maintained by intragastric infusion as a model for studying the endogenous loss of phosphorus in ruminants.

Mature sheep fitted with a rumen cannula and an abomasal catheter were used to evaluate whether sheep maintained by intragastric infusion could be used as a model for studying minimum endogenous phosporus loss in ruminants. In control periods the sheep received 1.29 g phosphorus day-1 by infusion and maintained phosphorus balance. The withdrawal of phosphorus from the infusate led to a reduction in the excretion of phosphorus to 6.4 mg kg liveweight-1 day-1, a level lower than that currently used to estimate maintenance phosphorus requirements. However, salivary phosphorus secretion, based on rumen phosphorus outflow, averaged only about 1.2 g day-1, a level which would be considered insufficient to meet rumen microbial requirements in a normally fed animal. Allowing the sheep access to a small amount of roughage, although contributing little additional phosphorus, greatly increased salivary phosphorus flow and increased their endogenous excretion of phosphorus to levels close to those used to estimate maintenance requirements. These results suggest that this technique may offer an alternative way of measuring minimum endogenous mineral loss to those currently in use.

Consumption of diets containing raw soya beans (Glycine max), kidney beans (Phaseolus vulgaris), cowpeas (Vigna unguiculata) or lupin seeds (Lupinus angustifolius) by rats for up to 700 days: effects on body composition and organ weights.

Feeding trials have been done with rats to assess the effects of long-term (700 d) consumption of diets based on raw cowpeas (Vigna unguiculata; moderate Bowman-Birk inhibitor content, low lectin content), lupin seeds (Lupinus angustifolius; low lectin and protease inhibitor content) or soya beans (Glycine max; high Kunitz inhibitor content, moderate Bowman-Birk inhibitor content, moderate lectin content) or diets containing low levels of raw kidney bean (Phaseolus vulgaris; high lectin content, low Bowman-Birk inhibitor content) on body weight and composition and organ weights. All the legume-based diets reduced feed conversion efficiency and growth rates during the initial 250 d. However, after 250 d the weight gains by rats given legume-based diets were similar to those of controls given the same daily feed intake. Long-term consumption of diets containing low levels of kidney bean significantly altered body composition of rats. The levels of lipid in the body were significantly reduced. As a result, carcasses of these rats contained a higher proportion of muscle/protein than did controls. Small-intestine relative weight was increased by short- and long-term consumption of the kidney-bean-based diet. However, the increase in relative pancreatic weight observed at 30 d did not persist long term. None of the other legume-based diets caused any significant changes in body composition. However, long-term exposure to a soya-bean- or cowpea-based diet induced an extensive increase in the relative and absolute weights of the pancreas and caused an increase in the incidence of macroscopic pancreatic nodules and possibly pancreatic neoplasia. Long-term consumption of the cowpea-, kidney-bean-, lupin-seed- or soya-bean-based diets by rats resulted in a significant increase in the relative weight of the caecum and colon.

The effect of high phosphorus intake on calcium and phosphorus retention and bone turnover in growing lambs.

Growing lambs were fed diets that just met their requirement for Ca but which supplied either 1 or 3 times their requirement for P and the effects on Ca and P retention and on bone turnover were monitored. Feeding the high P diet had no adverse effect on Ca and P absorption or retention or on bone formation rate. Bone resorption rate was a little higher in lambs fed the high P diet but there were no differences between treatments in plasma parathyroid hormone, 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 levels or in bone mineral content. It would appear from these results that feeding diets that are rich in P is unlikely to have any adverse effect on skeletal mineralization in the lamb provided that their minimum requirement for Ca is met.

Effects of low phosphate intake on bone and mineral metabolism and microbial protein synthesis in lambs.

Growing lambs were fed diets either low or adequate in phosphorus and their effects on Ca and P retention, bone formation and resorption and on ruminal microbial protein synthesis were measured. Plasma osteocalcin was used as an indicator of bone formation rate. Levels in plasma were lower in lambs fed the low P diet and were associated with a fall in plasma P concentration and reduced Ca and P retention. Low P intake had no effect on microbial protein synthesis or on bone resorption determined using urinary pyridinoline and deoxypyridinoline as markers. These results suggest that lack of mineral, rather than reduced ruminal microbial protein synthesis, is the main factor contributing to the reduction in bone formation rate seen in lambs fed low P diets.

Effects of a change in phosphorus requirement on phosphorus kinetics in the sheep.

An experiment was carried out to examine the effects of a change in P requirement, achieved by intravenous calcium loading, on intestinal phosphorus absorption, salivary phosphorus secretion and faecal endogenous phosphorus loss in adult sheep fitted with a rumen and duodenal cannula. Isotope dilution was used to measure faecal endogenous phosphorus loss while 103ruthenium phenanthroline and 51chromium-ethylenediamine tetra-acetic acid were used to measure duodenal phosphorus flow. The infusion of calcium chloride led to an increase in calcium and phosphorus retention, the increase in phosphorus retention being due to a reduction in faecal phosphorus excretion as a result of enhanced intestinal phosphorus absorption and reduced faecal endogenous phosphorus excretion. There was, however, no change in duodenal phosphorus flow or in the amount of phosphorus estimated to have been added to the digesta via the saliva. These results suggest that the increase in phosphorus retention seen in response to an increase in phosphorus requirement is largely achieved through an increase in intestinal absorptive efficiency and not through any reduction in endogenous phosphorus secretion into the gut.

Factors affecting urinary pyridinoline and deoxypyridinoline excretion in the growing lamb.

Changes in urinary pyridinium crosslink excretion and plasma osteocalcin and growth hormone levels were measured at 3-5 week intervals in lambs from 2-22 weeks of age, in relation to changes in metatarsal length. There were close correlations between pyridinium crosslink excretion and plasma growth hormone levels and live weight gain, but no direct relationship was seen between the rates of excretion of the pyridinium crosslinks and linear bone growth. Plasma osteocalcin levels were correlated with linear bone growth rate up to about 12 weeks of age but, thereafter, showed no correlation despite a continued decline in bone growth rate. In the young lamb, daily pyridinium crosslink excretion represented 1.3-2.9% of that in the body, declining to 0.06% of pool size in adult sheep.

Effects of acute acid loading on parathyroid hormone secretion and on urinary calcium and cAMP excretion in the growing lamb.

Growing lambs fed a diet containing NaHCO3 were made acidotic by intravenously infusing HCl at the rate of 1 mmol/min over a 4 h period. Acid infusion led to a fall in blood and urine pH and a prompt increase in urinary Ca excretion. This in turn led to a fall in plasma Ca concentration and a rise in parathyroid hormone (PTH) levels. Urinary cAMP excretion was unaffected by acid infusion. In separate experiments lambs made acidotic by feeding a diet containing NH4Cl were given infusions of PTH at the rate of 1 microgram/h. Infusion of the hormone was accompanied by a rise in plasma Ca and an increase rather than a decrease in urinary Ca excretion and no change in urinary cAMP excretion. These results point to the kidney as the primary site of response to acid loading in the lamb, a failure to reabsorb Ca in these conditions necessitating the release of PTH and an increase in bone resorption in order to maintain normal plasma Ca levels.

The effects of feeding diets containing either NaHCO3 or NH4Cl on indices of bone formation and resorption and on mineral balance in the lamb.

The effects of diet-induced changes in blood acid-base status on mineral retention has been studied in lambs fed diets containing either 1% NH4Cl or 2% NaHCO3. Balance measurements using 45Ca and 32P showed no difference between them in the amounts of dietary Ca and P absorbed from the gut. Retention of both minerals, however, was lower and their excretion in urine higher in those fed the acid diet. Plasma Ca and P levels were unaffected but parathyroid hormone and 1,25-dihydroxyvitamin D3 levels were higher in lambs on this diet while measurements of tartrate-resistant acid phosphatase and alkaline phosphatase levels in rib samples indicated an increase in osteoclast and a reduction in osteoblast activity in these lambs. Cell-mediated changes in bone turnover together with changes in urinary mineral loss would thus appear to be the major factors contributing to the lower rates of mineral retention seen in lambs fed acid diets.

Mechanisms of phosphate transport in sheep intestine and parotid gland: response to variation in dietary phosphate supply.

The transport of phosphate in intestinal brush-border membrane and parotid basolateral membrane vesicles isolated from sheep maintained on high and low phosphate diets have been studied. The mechanism of the transport of phosphate in the intestine is via a proton symporter whilst in the parotid gland it is effected by a Na+ coupled transporter. In sheep fed a low-P diet there is no change in the capacity of the parotid basolateral membrane to transport phosphate into the parotid end piece cells. This is in marked contrast to the response of the enterocyte brush-border membrane, where there is a significant enhancement of the capacity of the membrane to transport phosphate. We conclude that in sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate. This enhancement is not achieved by increases in the levels of circulating 1,25-dihydroxycholecalciferol.

The effect of variation in dietary protein or mineral supply on calcium and phosphorus metabolism in lactating ewes.

Two experiments are described in which changes in both nitrogen and mineral balance were monitored in ewes during lactation. In Expt 1, two groups (n 6) of ewes were fed on diets that were either high (15 g crude protein (N X 6.25; CP)/MJ metabolizable energy (ME)) or low (10 g CP/MJ ME) in protein content, and concurrent N and mineral balance studies were made at intervals during lactation with 45Ca and 32P being used to monitor faecal endogenous calcium and phosphorus losses. Ewes fed on the high-protein diet maintained a positive N balance during early lactation, whereas those fed on the low-protein diet were in negative N balance. Both groups, however, showed the same degree of negative Ca and P balance, with the amounts lost being directly related to milk yield. This indicates that loss of mineral from the skeleton at this time is not secondary to a loss of bone matrix due to a shortfall in dietary protein supply. In Expt 2, two groups of ewes (n 4) were fed on diets in late pregnancy that were either just adequate or generous in Ca and P supply relative to requirement (TCORN, 1990). After parturition both groups were fed on a diet which was formulated to meet their estimated Ca and P requirements for lactation. As in the previous experiment both groups were in negative Ca and P balance in early lactation and variation in dietary Ca and P supply during pregnancy had no effect on the extent of this loss. Alternative explanations for the cause of this loss of mineral from the skeleton are discussed.

The effects of feeding pelleted diets made from either coarsely or finely ground hay on phosphorus balance and on the partition of phosphorus excretion between urine and faeces in the sheep.

Mature sheep fitted with rumen and duodenal cannulae were fed pelleted diets made from hay that had been either coarsely or finely ground. The diets were supplemented with phosphorus and the effects on salivary phosphorus secretion, net intestinal phosphorus absorption and the route of excretion were examined. Changing the particle size of the diet had no effect on overall phosphorus balance but did affect the route of excretion with urine levels being higher and faecal levels lower in periods when the more finely ground diet was fed. This increase in urine excretion was not due to differences in phosphorus intake nor could it be attributed to increased net phosphorus absorption from the intestine. Salivary phosphorus secretion was, however, lower when the more finely ground diet was fed and it would appear that this change in the balance between that absorbed relative to its secretion back into the gut was the major factor contributing to the increased phosphorus excretion in the urine. The significance of these findings in relation to the high levels of phosphorus normally found in the urine of sheep fed concentrate diets compared to those fed roughage diets is discussed.

The effects of feeding either hay or grass diets on salivary phosphorus secretion, net intestinal phosphorus absorption and on the partition of phosphorus excretion between urine and faeces in the sheep.

Mature sheep fitted with ruminal and duodenal cannulas were fed either a pelleted hay or a pelleted grass diet with or without supplementary phosphorus. Salivary phosphorus secretion, net intestinal phosphorus absorption and the route of phosphorus excretion were determined. The route of excretion was markedly affected by diet with urinary excretion being much higher and faecal excretion lower when the grass diet was fed. These effects were not due to differences in phosphorus intake or to differences in net intestinal phosphorus absorption. Salivary phosphorus secretion was, however, lower when the grass diet was fed. The significance of these changes in relation to the control of phosphorus balance in ruminants is discussed.

The effect of potassium and magnesium infusion on plasma Mg concentration and Mg balance in ewes.

1. Concentrations of magnesium in plasma, the ionic concentration in rumen digesta supernatant fractions, Mg balance and electropotential differences were measured in three ewes which were fed on grass and supplemented with potassium and Mg by intraruminal infusion. 2. Mean plasma Mg concentrations were unaltered by combined K and Mg treatments, but fell (P less than 0.001) when K alone was infused. 3. The mean concentrations, in rumen digesta, of sodium and K varied reciprocally (P less than 0.001) with each other when K was infused, but were unaffected by Mg infusion. The mean Mg concentrations in rumen digesta fell (P less than 0.01) with K infusion but rose (P less than 0.001) with Mg infusion. 4. Absorption and excretion of Mg rose (P less than 0.001) when Mg intake was increased but was unaffected by K intake.