Antioxidant system response is modified by dietary fat in adipose tissue of metabolic syndrome patients

Metabolic syndrome (MetS) is associated with high oxidative stress, which is caused by an increased expression of NADPH-oxidase and a decreased expression of antioxidant enzymes in the adipose tissue. Our aim was to evaluate whether the quality and quantity of dietary fat can modify that process. A randomized, controlled trial conducted within the LIPGENE study assigned MetS patients to one of four diets for 12 wk each: (i) high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid (HMUFA), (iii) and (iv) two low-fat, high-complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids (LFHCC n3), or placebo (LFHCC). A fat challenge reflecting the same fatty acid composition as the original diets was conducted post-intervention. The intake of an HSFA meal induced a higher postprandial increase in gp91phox and p67phox mRNA levels than after the intake of HMUFA, LFHCC and LFHCC n-3 meals (all p-values < 0.05). The postprandial decrease in CAT, GPXs and TXNRD1 mRNA levels after the HSFA meal intake was higher than after the intake of HMUFA, LFHCC and LFHCC n-3 meals (all p-values < 0.05). The intake of an HSFA meal induced a higher postprandial increase in KEAP1 mRNA levels than after the consumption of the HMUFA (P = .007) and LFHCC n-3 (P = .001) meals. Our study demonstrated that monounsaturated fat consumption reduces oxidative stress as compared to saturated fat by inducing higher postprandial antioxidant response in adipose tissue, and thus, replacing SFA for MUFA may be an effective dietary strategy to reduce the oxidative stress in MetS patients and its pathophysiological consequences.     

Colon transcriptome is modified by a dietary pattern/atorvastatin interaction in the Ossabaw pig

Optimizing diet quality in conjunction with statin therapy is currently the most common approach for coronary artery disease (CAD) risk management. Although effects on the cardiovascular system have been extensively investigated, little is known about the effect of these interventions in the colon and subsequent associations with CAD progression. To address this gap, Ossabaw pigs were randomly allocated to receive, for a six-month period, isocaloric amounts of either a heart healthy-type diet (HHD; high in unrefined carbohydrate, unsaturated fat, fiber, supplemented with fish oil, and low in cholesterol) or a Western-type diet (WD; high in refined carbohydrate, saturated fat and cholesterol, and low in fiber), without or with atorvastatin therapy. At the end of the intervention period, colon samples were harvested, mucosa fraction isolated, and RNA sequenced. Gene differential expression and enrichment analyses indicated that dietary patterns and atorvastatin therapy differentially altered gene expression, with diet-statin interactions. Atorvastatin had a more profound effect on differential gene expression than diet. In pigs not receiving atorvastatin, the WD upregulated “LXR/RXR Activation” pathway compared to pigs fed the HHD. Enrichment analysis indicated that atorvastatin therapy lowered inflammatory status in the HHD-fed pigs, whereas it induced a colitis-like gene expression phenotype in the WD-fed pigs. No significant association was identified between gene expression phenotypes and severity of atherosclerotic lesions in the left anterior descending-left circumflex bifurcation artery. These data suggested diet quality modulated the response to atorvastatin therapy in colonic mucosa, and these effects were unrelated to atherosclerotic lesion development.     

Leptin levels in lines of mice developed by long-term divergent selection on fat content

The mouse lines were developed by long-term selection for fatness, after which the fat line (F) had about a 5-fold (23% vs 4%) higher fat percentage than the lean (L) line at 14 weeks; but the lines differed little in fat-free body weight. To assess the contribution of genetic changes in leptin hormone level to the selection response, plasma leptin levels were assayed in these lines in generation 60 and in an unselected control (C) from the same base population. With access to food prior to assay, the F, C and L lines had 16.5, 0.91 and 0.26 ng/ml leptin, respectively. In fasted animals these levels were much lower: 2.98, 0.171 and 0.0087 ng/ml, respectively. Thus the leptin levels differ greatly between the lines, with the fattest mice showing the highest level: almost 20 times higher than the control and 60-300 times higher than the L line. These correlated selection effects are an order of magnitude greater than the direct selection response, and believed to be much larger than seen for any hormonal or other trait. Correlations between leptin level and fat amount were high (over 0.86) in fed or fasted animals of the F line, indicative of leptin resistance.     

GDF-3 is an adipogenic cytokine under high fat dietary condition

Growth differentiation factor 3 (GDF-3) is structurally a bone morphogenetic protein/growth differentiation factor subfamily member of the TGF-beta superfamily. GDF-3 exhibits highest level of expression in white fat tissue in mice and is greatly induced by high fat diet if fat metabolic pathway is blocked. To identify its biological function, GDF-3 was overexpressed in mice by adenovirus mediated gene transfer. Mice transduced with GDF-3 displayed profound weight gain when fed with high fat diet. The phenotypes included greatly expanded adipose tissue mass, increased body adiposity, highly hypertrophic adipocytes, hepatic steatosis, and elevated plasma leptin. GDF-3 stimulated peroxisome proliferator activated receptor expression in adipocytes, a master nuclear receptor that controls adipogenesis. However, GDF-3 was not involved in blood glucose homeostasis or insulin resistance, a condition associated with obesity. In contrast, similar phenotypes were not observed in GDF-3 mice fed with normal chow, indicating that GDF-3 is only active under high lipid load. Thus, GDF-3 is a new non-diabetic adipogenic factor tightly coupled with fat metabolism.     

Discriminating between energetic content and dietary composition as an explanation for dietary restriction effects

A reduction in dietary calories has been shown to prolong life span in a wide variety of taxa, but there has been much debate about confounding factors such as nutritional composition of the diet, or reallocation of nutrients from reduced reproduction. To disentangle the contribution of these different mechanisms to extension of life span, we study the effect of caloric restriction on longevity and fecundity in two species of sugar-feeding parasitoid wasps. They have a simple diet that consists of carbohydrates only, and they do not resorb eggs, which rules out the proposed alternative explanations for beneficial effects of caloric restriction. Two caloric restriction treatments were applied: first, dietary dilution to investigate the effect of carbohydrate concentration in the diet; and second, intermittent feeding to examine the effect of feeding frequency on longevity and fecundity. Only the dietary dilution treatment showed an effect of caloric restriction with the highest longevity recorded at 80% sucrose (w/v). No effect of dietary regime was found on fecundity. We also measured the weight increase of the parasitoids after feeding to obtain an estimate of consumption. A constant quantity of the sugar solution was consumed in all dietary dilution treatments, hence caloric intake was proportional to sucrose concentrations. Although the present study does not disqualify the relevance of nutrient composition in other species, our data unequivocally demonstrate that caloric restriction alone is sufficient to extend life span and invalidate alternative explanations.     

Leptin regulates energetic tradeoffs between body fat and humoural immunity

Mounting an immune response requires a relatively substantial investment of energy and marked reductions in energy availability can suppress immune function and presumably increase disease susceptibility. We have previously demonstrated that a moderate reduction in energy stores via partial surgical lipectomy (LIPx) impairs humoural immunity of Siberian hamsters (Phodopus sungorus). Here we tested the hypothesis that LIPx-induced decreases in immunity are mediated by changes in the adipose tissue hormone leptin. Hamsters received bilateral surgical removal of inguinal white adipose tissue (IWATx) or sham surgeries (Sham). Half the animals in each group received osmotic minipumps containing murine leptin (0.5mulh-1 for 10 days) whereas the remaining animals received minipumps containing vehicle alone; all animals were subsequently challenged with the novel antigen keyhole limpet haemocyanin (KLH). In general, serum leptin and anti-KLH antibodies were significantly correlated with one another with higher levels generally indicating enhanced immunity. In addition, IWATx hamsters had significantly lower serum anti-KLH IgG compared with sham animals. Exogenous leptin, however, attenuated LIPx-induced immune suppression but did not affect humoural immunity in sham animals. These results suggest that reductions in energy availability lead to impairments in humoural immunity and that leptin can serve as a neuroendocrine signal between body fat and immunity regulating humoural immune responses.     

Effect of ambient temperature on the productive and carcass traits of growing rabbits divergently selected for body fat content

Rabbits are particularly sensitive to heat stress which can affect productive performance, with rabbit breed/line possibly playing a role on the response to this condition. The study aimed at evaluating the effect of different ambient temperatures on the live performance and carcass traits of growing rabbits divergently selected for total body fat content. The two genetic lines (Lean and Fat) were selected based on the total body fat content estimated by computer tomography during five generations. From birth to slaughter (13 weeks of age), the rabbits were housed in two rooms where the temperature was controlled with air conditioners: in the control room the average ambient temperature was 20 °C and in the high temperature room it was 28 °C. After weaning (35 d), 60 Lean and 60 Fat rabbits/room were housed by two in wire-mesh cages and fed ad libitum with commercial pellets. The BW and feed intake (FI) were measured at 5, 7, 9, 11 and 13 weeks of age to calculate the daily weight gain (DWG) and feed conversion ratio (FCR). Mortality was recorded daily. At the end of the experiment, rabbits were slaughtered and carcass traits were measured. Mortality was independent of temperature and line. The temperature significantly influenced the FI, DWG, BW and the fat deposits: they were lower at higher ambient temperature. The effect of temperature differed according to the rabbits' total body fat content. At control temperature, the FI (165 vs 155 g/day; P < 0.05) and FCR (4.67 vs 4.31; P < 0.05) were higher in Fat rabbits, which also had more perirenal (36.2 vs 23.1 g; P < 0.05) and scapular fat (10.8 vs 7.1 g; P < 0.05). At high temperature, no differences in fat depots (14.5 vs 9.8 g; 5.3 vs 3.5 g) were found between the two lines. It can be concluded that temperature × genetic line interaction had an important role in productive and carcass traits, as the effect of temperature differs between Lean and Fat rabbits.     

Relationship between prostate-specific antigen levels and ambient temperature

We examined the association between prostate-specific antigen (PSA) and daily mean ambient temperature on the day of the test in healthy men who had three annual checkups. We investigated 9,694 men who visited a hospital for routine health checkups in 2007, 2008, and 2009. Although the means and medians of ambient temperature for the three years were similar, the mode in 2008 (15.8 °C) was very different from those in 2007 and 2009 (22.4 °C and 23.2 °C). After controlling for age, body mass index, and hematocrit, a multiple regression analysis revealed a U-shaped relationship between ambient temperature and PSA in 2007 and 2009 (P?<?0.001 and P?=?0.004, respectively), but not in 2008 (P?=?0.779). In 2007, PSA was 13.5 % higher at 5 °C and 10.0 % higher at 30 °C than that at 18.4 °C (nadir). In 2009, PSA was 7.3 % higher at 5 °C and 6.8 % at 30 °C compared with the level at 17.7 °C (nadir). In logistic regression analysis, a U-shaped relationship was found for the prevalence of a higher PSA (> 2.5 ng/mL) by ambient temperature, with the lowest likelihood of having a high PSA at 17.8 °C in 2007 (P?=?0.038) and 15.5 °C in 2009 (P?=?0.033). When tested at 30 °C, there was a 57 % excess risk of having a high PSA in 2007 and a 61 % higher risk in 2009 compared with those at each nadir temperature. We found a U-shaped relationship between PSA and ambient temperature with the lowest level of PSA at 15–20 °C.     

Manganese absorption and retention in rats is affected by the type of dietary fat

There is evidence that manganese (Mn) metabolism may be altered by the form and amount of dietary fat. Also, iron (Fe) absorption is greater with saturated fats, as compared to polyunsaturated fatty acids (PUFAs). The absorption of Fe and Mn are interrelated in many aspects; therefore, the form of dietary fat may indirectly alter Mn absorption. The reported studies were conducted to determine whether saturated fat, as compared to unsaturated fat, affected Mn absorption, retention, and metabolism. In experiment I, adult rats were fed diets containing either 0.7 or 100.4 μg/g Mn with the fat source as high-linoleic safflower oil or stearic acid. After 2 wk of equilibration, the animals were fed a test meal of ⁵⁴Mn followed by whole-body counting for 10 d. Manganese absorption was significantly (p<0.05) lower in the stearic acid group (0.9–4.8%) than in the safflower oil group (20–33.8%); however, the biological half-life was shorter in the safflower oil group. Retention of ⁵⁴Mn and total Mn was always significantly (p<0.05) greater in the safflower oil group when dietary Mn was low, but it was the same when dietary Mn was high. In experiment II, weanling rats were fed 1.3, 39.3, or 174.6 μg Mn/g and either stearate, high-oleic safflower oil or high-linoleic safflower oil for 8 wk. Long-term feeding of the stearate and low Mn-containing diet resulted in a significant (p<0.0001) reduction in heart superoxide dismutase activity and kidney and liver Mn concentrations compared to the other diets. These data show that stearic acid inhibitits Mn absorption, but it may not inhibit Mn retention when dietary Mn is high. The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination. Mention of a trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable.     

Genetic interaction with temperature is an important determinant of nematode longevity

As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer‐lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature‐specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature‐specific longevity is more the rule than the exception. By measuring the lifespans of worms with single modifications reported to be important for longevity at 15, 20, or 25 °C, we find that the effect of each modification on lifespan is highly dependent on temperature. Our results suggest that genetics play a major role in temperature‐associated longevity and are consistent with the hypothesis that while aging in C. elegans is slowed by decreasing temperature, the major cause(s) of death may also be modified, leading to different genes and pathways becoming more or less important at different temperatures. These differential mechanisms of age‐related death are not unlike what is observed in humans, where environmental conditions lead to development of different diseases of aging.     

Blood content of tyrosine is an index of glucocorticoid action on metabolism

Glucocorticoid hormones directly or indirectly control virtually all metabolic and physiological processes. Glucocorticoids are also shown to act on a multitude of genes, enzyme systems, and proinflammatory factors, but for these hormones there is no representative index of action on metabolism similar to glucose content in blood for insulin. The absence of such an index prevents the assessment of tissue provision with these hormones under various conditions and seems to be an essential cause of complications associated with the clinical use of glucocorticoid preparations. Considering specific features of tyrosine metabolism and data obtained experimentally and on a clinical model (adrenalectomy in rats and substitution therapy in endocrine disease), blood content of this amino acid seems promising as such an index. Based on comparing results of glucocorticoid treatment in patients with systemic lupus erythematosus with changes in their blood tyrosine contents, the pharmacological effect of glucocorticoid preparations is suggested to be mainly due to compensating a relative shortage of these hormones.     

Mechanism of interaction between cellulase action and applied shear force, an hypothesis

An overview is given of what is known in literature concerning the structure of both cellulose and cellulase enzymes and the enzymatic degradation of cellulose. Based on this knowledge, a hypothesis is formulated about the relation between cellulase performance and required applied shear force on the fabric. In short, the specific cellulase activity is highest on the flexible amorphous cellulose when compared to that with the more rigid crystalline cellulose. When applying cellulase activity on damaged, fuzzy fabric, the connection point of cellulose material oriented away from the fiber axis, which is partly amorphous due to the damage, will be turned again to a more rigid, mainly crystalline structure. Due to this shift, this connection point will function as a primary point of application for shear force, resulting in removal of the fuzz.     

Tissue fatty acid deposition is influenced by an interaction of dietary oil source and energy intake level in rats

To investigate the net tissue fatty acid deposition in response to graded levels of energy restriction and modification of diet fatty acid composition, rats were randomly assigned into four dietary groups and fed for 10 weeks diets containing 40% as energy of either fish, safflower, or olive oil, or beef tallow, consumed ad libitum or energy restricted to 85% or 68% of ad libitum intake by reducing diet carbohydrate content. An additional eight rats were killed before the diet regimen, to provide baseline data from which fatty acid deposition rates were calculated. Body weight, and heart, liver and fat mass gains were decreased with energy restriction (P<0.001). Olive oil feeding resulted in higher body weight gain (P < 0.03) than tallow feeding, whereas fish oil feeding was associated with highest (P < 0.007) liver weight and lowest (P < 0.03) fat mass gains. Energy deficit-related differences in the deposition of stearic, linoleic, arachidonic, and docosahexaenoic acids in heart and palmitic and docosahexaenoic acids in liver were dependent on the dietary oil consumed (P < 0.03). Similarly, interactive effects of restricted food intake and dietary oil type were found in the gain of palmitic, stearic, oleic, and linoleic acids in adipose tissue (P < 0.01) when expressed in relation to the amount of each fatty acid consumed. These data suggest that energy intake level can influence the deposition pattern, as well as oxidation rate, of tissue fatty acids as a function of tissue type, fatty acid structure, and dietary fatty acid composition.     

Direct interaction between EFL1 and SBDS is mediated by an intrinsically disordered insertion domain

Removal of anti-association factor, Tif6 (eIF6), by elongation factor-like 1 (EFL1) and Shwachman–Bodian–Diamond syndrome (SBDS) protein is a critical step in the late stage of ribosome maturation. Although EFL1 is known to have GTPase activity that is stimulated by SBDS, how they cooperatively trigger dissociation of Tif6 from the ribosome remains to be elucidated. In the present study, the interaction between EFL1 and SBDS was analyzed by size exclusion chromatography, gel shift assay, and isothermal titration calorimetry (ITC). The results showed that EFL1 interacted directly with SBDS. ITC experiments using domain-truncated mutants showed that the interaction between EFL1 and SBDS is governed by the insertion domain of EFL1 and domains II–III of SBDS. Circular dichroism spectroscopy showed that the insertion domain of EFL1 has a random structure in the absence of SBDS, whereas the disadvantageous entropy change observed on ITC suggested a fixed conformation coupled with complex formation with SBDS. Based on these observations together with those reported previously, we propose roles of EFL1 and SBDS in ribosomal maturation.     

The collagenolytic action of MMP-1 is regulated by the interaction between the catalytic domain and the hinge region

The role of the hinge region in the unwinding and cleavage of type I collagen by interstitial collagenase (MMP-1) has been studied at 37 °C and pH 7.3. The collagenolytic processing by MMP-1 displays a very similar overall rate for both chains of collagen I, even though the affinity is higher for the α-1 chain and the cleavage rate is faster for the α-2 chain. MMP-1 binding to collagen I brings about a significant unwinding of the triple-helical arrangement only after the first cleavage step of the α-1 and α-2 chains. The proteolytic processing by wild-type MMP-1 on a synthetic substrate and collagen I has been compared with that observed for site-directed mutants obtained either by truncating the hinge region (∆255–272) or by individually replacing the conserved amino acids Val268, Gly272, and Lys277 of the hinge region with residues observed for the corresponding position in stromelysin-1 (MMP-3), a noncollagenolytic metalloproteinase. The ∆256–272 mutant has no collagenolytic activity, clearly demonstrating the crucial role of this region for the enzymatic processing of collagen I. However, among various mutants investigated, only Gly272Asp shows a dramatically reduced enzymatic activity both on the synthetic substrate and on collagen I. This effect, however, is clearly related to the substituting residue, since substitution of Ala or Asn for Gly272 does not have any effect on the kinetic properties of MMP-1. These data suggest that the substrate specificity of MMP-1 is dictated by the reciprocal structural relationships between the catalytic domain and the carboxy-terminal domain through the conformational arrangement of the hinge region.     

Retracted: Notch activation is regulated by an interaction between hCLP46 and chaperone protein calnexin

Retraction: The following article from Cell Biochemistry and Function, "Notch activation Is regulated by interaction between hCLP46 and the chaperone protein calnexin" by Xiaoqin Feng and Lixin Liu, published online on 3 April 2012 in Wiley Online Library (www.wileyonlinelibrary.com), has been retracted with agreement from the authors, the journal Editor, Nigel Loveridge, and John Wiley & Sons Ltd. The retraction has been agreed because the paper was submitted without approval from the co-author, Lixin Liu, and contains data that requires further experimentation in order to support the conclusions fully. Reference Feng, X. and Liu, L. (2012), Notch activation is regulated by an interaction between hCLP46 and chaperone protein calnexin. Cell Biochem. Funct. doi: 10.1002/cbf.2825.     

Insulin binding to liver nuclei from lean and obese mice is altered by dietary fat.

Insulin binding to the plasma membrane is known to be altered by modifying the membrane composition through dietary treatment. As insulin binding receptors are also present on nuclear membrane, this study was undertaken to investigate if specific binding of insulin to the liver nuclei is altered by diet. 8-wk-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low polyunsaturated-to-saturated (P/S) fatty acid ratio for 4 wk. Liver nuclei were prepared, insulin binding was measured and nuclear phospholipids were isolated for lipid analysis. Insulin binding was highest in nuclei prepared from lean mice fed a high P/S diet. Specific binding of insulin to nuclei prepared from obese mice was also increased by the high P/S diet, but to a lesser extent compared to lean mice. Feeding a high P/S diet increased polyunsaturated fatty acid content of membrane phospholipids from both lean and ob/ob mice. Obese mice were characterized by higher levels of arachidonic acid and lower levels of linoleic acid in phosphatidylcholine. The present study establishes that insulin binding to liver nuclei is increased by feeding a high P/S diet, and that insulin binding to liver nuclei from obese mice is lower than from lean mice.