Liver function parameters,cholesterol, and phospholipid α-linoleic acid are associated with adipokine levels in overweight and obese adults

Dysregulation of adipose hormones in obesity has been associated with the hastened development of metabolic syndrome and associated chronic disease sequalae including cardiovascular disease and type 2 diabetes mellitus. This study aims to identify common biochemical and anthropometric markers that impact adipose hormones, including adiponectin and leptin. Based on previous literature, it was hypothesized that these would be adversely impacted by liver function parameters, and adiponectin levels would be positively correlated with phospholipid Ω-3 fatty acids. Forty nondiabetic adult subjects (body mass index, ≥25.0 kg/m²) were recruited. Fasting plasma samples were taken to assess adipokine levels, glucose metabolism, electrolytes, liver enzymes, and blood lipids. Basic anthropometric measurements were also recorded. Adiponectin levels were positively correlated with high-density lipoprotein cholesterol and negatively correlated with anthropometric measures, insulin, liver enzymes, triglycerides, and very low–density lipoprotein cholesterol but not body mass index. Conversely, plasma leptin levels were positively correlated with anthropometric measures, C-reactive protein, high-density lipoprotein cholesterol, and plasma phospholipid proportions of Ω-3 α linoleic acid but inversely correlated with creatinine levels. These results support other data regarding correlations between adiponectin and relative adipose distribution. Correlations with specific liver enzymes may indicate that adiponectin levels are tied to fatty acid deposition in the liver; however, liver/kidney damage though further mechanistic clarification is required. Leptin levels were associated with measures of adiposity but not liver enzymes. Each of these variables, along with blood lipids, may serve as potential future therapeutic targets for the prevention and management of obesity and related comorbidities.     

Effect of 6 weeks' consumption of β-glucan-rich oat products on cholesterol levels in mildly hypercholesterolaemic overweight adults

Several regulatory bodies have approved a health claim on the cholesterol-lowering effects of oat β-glucan at levels of 3·0 g/d. The present study aimed to test whether 1·5 g/d β-glucan provided as ready-to-eat oat flakes was as effective in lowering cholesterol as 3·0 g/d from oats porridge. A 6-week randomised controlled trial was conducted in eighty-seven mildly hypercholesterolaemic ( ≥ 5 mmol/l and < 7·5 mmol/l) men and women assigned to one of three diet arms (25 % energy (E%) protein; 45 E% carbohydrate; 30 E% fat, at energy requirements for weight maintenance): (1) minimal β-glucan (control); (2) low-dose oat β-glucan (1·5 g β-glucan; oats low - OL) or (3) higher dose oat β-glucan (3·0 g β-glucan; oats high - OH). Changes in total cholesterol and LDL-cholesterol (LDL-C) from baseline were assessed using a linear mixed model and repeated-measures ANOVA, adjusted for weight change. Total cholesterol reduced significantly in all groups ( - 7·8 (sd 13·8) %, - 7·2 (sd 12·4) % and - 5·5 (sd 9·3) % in the OH, OL and control groups), as did LDL-C ( - 8·4 (sd 18·5) %, - 8·5 (sd 18·5) % and - 5·5 (sd 12·4) % in the OH, OL and control groups), but between-group differences were not significant. In responders only (n 60), β-glucan groups had higher reductions in LDL-C ( - 18·3 (sd 11·1) % and - 18·1 (sd 9·2) % in the OH and OL groups) compared with controls ( - 11·7 (sd 7·9) %; P = 0·044). Intakes of oat β-glucan were as effective at doses of 1·5 g/d compared with 3 g/d when provided in different food formats that delivered similar amounts of soluble β-glucan.     

High α-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats

Prostaglandins (PG) have a regulatory influence on ovulation. α-Linolenic acid (ALA) vs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differently influence PG biosynthesis. Whereas high EPA/DHA reduces PGE₂, enhancing ovulation, we hypothesized that ALA would not affect ovulation. Our objective was to determine the effect of low and high ALA intake vs EPA/DHA on ovarian phospholipids, ovulation, and PG synthesis in rats. Following 27 days on diet and ovulation induction, ovaries were isolated and analyzed in 22 pups per diet. Ovarian phospholipid (n-3) polyunsaturated fatty acid (PUFA) incorporation increased with EPA/DHA ingestion. With significant ovarian (n-3) PUFA or EPA (P < .05) enrichment in the high–n-3 PUFA diets, ova release increased. Although high ALA did not enrich total (n-3), it increased ova release and tissue EPA over low ALA or control. Dietary EPA/DHA more effectively reduced ovarian arachidonic acid levels than dietary ALA. Dietary ALA increased PGF and very high intake reduced PGE, whereas EPA/DHA did not alter PGE or PGF. Enhanced ova release with high (n-3) PUFA intake may be induced via multiple mechanisms including reduced ovarian arachidonic acid. Significant ovarian retention of EPA and DHA enhanced ovulation with unchanged total PGE and PGF. Lack of change in PGE may have resulted from reduced PGE₂ combined with increased PGE₃. When EPA alone was elevated, PGE was reduced, whereas PGF was increased. Results indicate that very high ALA intake enhances ovulation similar to very high EPA/DHA ingestion, an effect potentially mediated via similar patterns of PGF₂α and PGE₂ synthesis.     

Dietary intakes of α-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men

Investigations suggest a protective role of n-3 polyunsaturated fatty acids (PUFA) but opposing roles of n-6 PUFA in inflammation, but the effects in vivo the human are not clear. We therefore tested the hypothesis that higher intakes of n-3 PUFA and n-6 PUFA are associated with lower levels of inflammation among a population consuming a diet high in PUFA. This study aimed to assess the association between PUFA intake and serum C-reactive protein (CRP) concentrations in a group of Japanese employees. The study subjects were 300 men and 211 women aged 21 to 67 years working in 2 municipal offices of Japan. We measured the serum high-sensitivity CRP concentrations by the latex agglutination nephelometry method and assessed dietary habits by a validated self-administered diet history questionnaire. We analyzed the data using multiple linear regression analysis with adjustment for potential confounding variables. Mean serum CRP concentrations tended to decrease as the intake of eicosapentaenoic acid, docosahexaenoic acid, or their combination increased in men and women, although none of these relationships was statistically significant. In men, there were statistically significant inverse relationships between dietary intake of n-3 or n-6 PUFA and serum CRP concentrations (P for trend = .03 and .008, respectively). Among specific PUFA, only α-linolenic acid and linoleic acid showed clear inverse relationships (P for trend = .001 and .003, respectively) in men. The results suggest that increased intake of not only α-linolenic acid (n-3 PUFA) but also linoleic acid (n-6 PUFA) has a beneficial effect on systemic inflammation in men.     

β-Hydroxy-β-methylbutyrate facilitates PI3K/Akt-dependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor α/interferon γ–induced MuRF-1 expression in C2C12 cells

β-Hydroxy-β-methylbutyrate (HMB) prevents deleterious muscle responses under pathological conditions, including tumor- and chronic steroid therapy–related muscle losses. Here, we investigated the hypothesis that HMB may modulate the balance between protein synthesis and degradation in the PI3K/Akt-mediated mammalian target of rapamycin (mTOR) and FoxO1/FoxO3a-dependent mechanisms in differentiated C2C12 muscle cells. We also tested the effect of HMB on the expression of MuRF-1 and atrogin-1 in response to the inflammatory stress. β-Hydroxy-β-methylbutyrate up-regulated phosphorylation of Akt and mTOR, and these effects were completely abolished in the presence of PI3K inhibitor LY294002. β-Hydroxy-β-methylbutyrate also up-regulated FoxO1 and FoxO3a phosphorylation, and these changes were inhibited by LY294002. Although, unexpectedly, HMB failed to reduce the expressions of atrophy-related atrogin-1 messenger RNA and the protein response to the proinflammatory cytokines tumor necrosis factor α plus interferon γ, HMB did attenuate the MuRF-1 expression. Thus, HMB appears to restore the balance between intracellular protein synthesis and proteolysis, likely via activation of the PI3K/Akt-dependent mTOR and FoxO1/FoxO3a signaling pathway and the reduction of tumor necrosis factor α/interferon γ–induced MuRF-1 expression, thereby ameliorating aging-related muscle atrophy.     

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate–activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.     

Phosphatidylserine inhibits inflammatory responses in interleukin-1β–stimulated fibroblast-like synoviocytes and alleviates carrageenan-induced arthritis in rat

Recently, phosphatidylserine (PS) has received attention for its anti-inflammatory effect; however, the molecular mechanisms of its action have not been fully understood. Thus, we hypothesized that PS might have antiarthritic and anti-inflammatory effects. To test this hypothesis, the in vitro anti-inflammatory effect of soybean-derived PS was tested on interleukin (IL)-1β–stimulated fibroblast-like synoviocytes from rheumatoid arthritis patients (RA-FLS) by measuring the levels of IL-6, IL-8, prostaglandin E₂, and vascular endothelial growth factor by enzyme-linked immunosorbent assay. The analgesic and antiarthritic activities of PS were investigated in rat models of carrageenan-induced acute paw pain and arthritis. The former was evaluated with a paw pressure test; the latter, by measuring paw volume and weight distribution ratio. In addition, the participation of mitogen-activated protein kinase signaling in the anti-inflammatory and antiarthritic effects of PS was investigated in RA-FLS. Phosphatidylserine inhibited the production of inflammatory mediators IL-6; IL-8; vascular endothelial growth factor; and, in particular, prostaglandin E₂ in IL-1β–stimulated RA-FLS. These effects were associated with abrogation of inhibitor of nuclear factor–κBα phosphorylation and suppression of p38 and c-jun amino terminal kinase but not extracellular signal–regulated kinase 1/2 phosphorylation. In rats, PS also showed a significant inhibitory effect on arthritic and nociceptive symptoms induced by carrageenan. These findings suggest that PS has anti-inflammatory and antiarthritic effects in vitro and in in vivo animal models; thus, PS should be further studied to determine its potential use as either a pharmaceutical or dietary supplement for alleviating arthritic symptoms.     

α-Tocopherol,ascorbic acid,and β-carotene protect against oxidative stress but reveal no direct influence on p53 expression in rats subjected to stress

We hypothesized that α-tocopherol, ascorbic acid, and β-carotene, either applied individually or in combination, would modulate redox homeostasis and affect the regulation of genes involved in DNA repair under stress conditions. To test this hypothesis, we analyzed the influence of these vitamins, either supplied individually or in combination, on the plasma lipid peroxide level and the hepatic level of 8-hydroxy-2′-deoxyguanosine in rats. We also evaluated the expression of p53 and Mdm2 protein in the intestinal epithelium, as these proteins are involved in the cellular regulation of DNA damage repair. Male Wistar rats (n = 112) were supplemented with α-tocopherol (2 mg), ascorbic acid (12 mg), and β-carotene (1 mg), both individually and in combination, for 14 days; 32 control rats were treated with placebo. Half of the animals in each group (n = 8) were subjected to 15-minute treadmill running at 20 m/min to cause exercise-induced oxidative stress. A statistically significant reduction in lipid peroxide levels was observed in the plasma of rats subjected to exercise and given 2 or 3 of the antioxidants (P < .0001). Exercise, as well as coadministration of the antioxidants, had no significant effect on the amount of DNA damage. Downward trends in the level of p53 protein expression were observed both in exercised and nonexercised animals, especially when the studied vitamins were administered in combination. Our findings suggest that α-tocopherol, ascorbic acid, and β-carotene, when given concurrently, have primarily antioxidant effects on lipids under stress but do not significantly affect the regulation of p53 gene expression.     

Dietary (1,3/1,6)-β-d-glucan decreases transforming growth factor β expression in the lung of the neonatal piglet

Identification and characterization of compounds that enhance the growth, development, and health of infants who are not breastfed continues to be a goal for nutritional science. This study explored the effects of one dietary component, (1,3/1,6)-β-d-glucan (Wellmune WGP), on lung immune development in the neonatal piglet. The hypothesis was that supplementation with WGP, a pathogen-associated molecular pattern, would enhance pathogen-responsive elements of the immune system, for instance, by increasing the size of the cytotoxic T-cell population or the expression of inflammatory cytokines. Piglets were fed a control formula or formula plus WGP at 1.8, 18, or 90 mg/kg body weight per day. Serum, thoracic lymph nodes (TLNs), mediastinal lymph nodes, and lung were collected at days 7 or 21. Immune parameters including tissue messenger RNA (mRNA) expression and T-cell phenotypes were analyzed. Normal developmental changes were observed, with a decrease in T-helper cells and an increase in cytotoxic T cells in both TLN and mediastinal lymph node, but there was no effect of WGP. Dietary WGP reduced the mRNA expression of transforming growth factor (TGF) β2 and tended to reduce the mRNA expression of TGF-β1 in lung tissue. With the exception of reducing TGF-β mRNA in the lung and tending to decrease the ratio of T helper to cytotoxic T cell in the TLN, dietary WGP did not affect lung-associated adaptive immunity in piglets.     

Inhibition of betaine-homocysteine S-methyltransferase in rats causes hyperhomocysteinemia and reduces liver cystathionine β-synthase activity and methylation capacity

Methylation of homocysteine (Hcy) by betaine-Hcy S-methyltransferase (BHMT) produces methionine, which is required for S-adenosylmethionine (SAM) synthesis. We have recently shown that short-term dietary intake of S-(Δ-carboxybutyl)-dl-Hcy (D,L-CBHcy), a potent and specific inhibitor of BHMT, significantly decreases liver BHMT activity and SAM concentrations but does not have an adverse affect on liver histopathology, plasma markers of liver damage, or DNA methylation in rats. The present study was designed to investigate the hypothesis that BHMT is required to maintain normal liver and plasma amino acid and glutathione profiles, and liver SAM and lipid accumulation. Rats were fed an adequate (4.5 g/kg methionine and 3.7 g/kg cystine), cysteine-devoid (4.5 g/kg methionine and 0 g/kg cystine), or methionine-deficient (1.5 g/kg methionine and 3.7 g/kg cystine) diet either with or without L-CBHcy for 3 or 14 days. All rats fed L-CBHcy had increased total plasma Hcy (2- to 5-fold) and reduced liver BHMT activity (>90%) and SAM concentrations (>40%). S-(Δ-carboxybutyl)-l-Hcy treatment slightly reduced liver glutathione levels in rats fed the adequate or cysteine-devoid diet for 14 days. Rats fed the methionine-deficient diet with L-CBHcy developed fatty liver. Liver cystathionine β-synthase activity was reduced in all L-CBHcy-treated animals, and the effect was exacerbated as time on the L-CBHcy diet increased. Our data indicate that BHMT activity is required to maintain adequate levels of liver SAM and low levels of total plasma Hcy and might be critical for liver glutathione and triglyceride homeostasis under some dietary conditions.     

Oligonol improves memory and cognition under an amyloid β25-35–induced Alzheimer's mouse model

Alzheimer's disease is an age-dependent progressive neurodegenerative disorder that results in impairments of memory and cognitive function. It is hypothesized that oligonol has ameliorative effects on memory impairment and reduced cognitive functions in mice with Alzheimer's disease induced by amyloid β_25-35 (Aβ_25-35) injection. The protective effect of an oligonol against Aβ_25-35-induced memory impairment was investigated in an in vivo Alzheimer's mouse model. The aggregation of Aβ_25-35 was induced by incubation at 37°C for 3 days before injection into mice brains (5 nmol/mouse), and then oligonol was orally administered at 100 and 200 mg/kg of body weight for 2 weeks. Memory and cognition were observed in T-maze, object recognition, and Morris water maze tests. The group injected with Aβ_25-35 showed impairments in both recognition and memory. However, novel object recognition and new route awareness abilities were dose dependently improved by the oral administration of oligonol. In addition, the results of the Morris water maze test indicated that oligonol exerted protective activity against cognitive impairment induced by Aβ_25-35. Furthermore, nitric oxide formation and lipid peroxidation were significantly elevated by Aβ_25-35, whereas oligonol treatment significantly decreased nitric oxide formation and lipid peroxidation in the brain, liver, and kidneys. The present results suggest that oligonol improves Aβ_25-35-induced memory deficit and cognition impairment.     

High-fat diet-induced reduction of peroxisome proliferator–activated receptor-γ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome

Animal models of type 2 diabetes exhibit reduced peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.     

Race differences in the relation of vitamins A,C, E,and β-carotene to metabolic and inflammatory biomarkers

Using archival data, we conducted a secondary analysis to examine race differences in the relation of serum vitamins A, C, E and β-carotene to insulin resistance (IR), fasting insulin and glucose, high sensitivity C-reactive protein (hs-CRP), and leukocyte count in 176 non-smoking, healthy, white, and African American (AA) adults aged 18 to 65 years (48% women, 33% AA). We hypothesized that micronutrient concentrations would be associated with early risk markers of cardiometabolic diseases in a race-dependent manner. Fasting blood samples were analyzed for micronutrients, insulin, glucose, hs-CRP, and leukocyte count. Insulin resistance was estimated using the homeostatic model assessment. After adjusting for age, body mass index, gender, educational level, use of vitamin supplements, alcohol intake, leisure time physical activity, menopausal status, and total cholesterol, we observed that β-carotene was significantly associated with insulin resistance and fasting insulin in a race-dependent manner. Among AA, lower β-carotene levels were associated with higher estimates of insulin resistance and fasting insulin; whereas, these same associations were not significant for whites. Race also significantly moderated the relation of vitamin C to leukocyte count, with lower vitamin C being associated with higher leukocyte count only in AA but not whites. For all subjects, lower β-carotene was associated with higher hs-CRP. In AA, but not whites, lower levels of β-carotene and vitamin C were significantly associated with early risk markers implicated in cardiometabolic conditions and cancer. Whether or not lower levels of micronutrients contribute uniquely to racial health disparities is a worthwhile aim for future research.     

α-Lipoic acid reduces matrix metalloproteinase activity in MDA-MB-231 human breast cancer cells

α-Lipoic acid (LA), a naturally occurring molecule in animal and plant cells, is a potent antioxidant that reportedly exerts beneficial effects on cell proliferation and apoptosis in various cancer cell lines. However, the molecular mechanisms behind the antimetastatic property of LA are not well understood. The present study investigates the effect of LA on metastasis in a cell system. Our hypothesis is that LA inhibits metastasis via inhibition of matrix metalloproteinase (MMP) in vitro. MDA-MB-231 cells, a human breast cancer cell line, were treated with various concentrations of LA (0, 250, 500, or 1000 μmol/L) to measure metastasis, MMP activity, and mRNA expression. The viability of cells was examined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The effect of LA on metastasis was evaluated using the motility, migration, and invasion assay in vitro. The activity and mRNA expression of MMP-2 and MMP-9 were measured. After LA treatment, cell motility and cell migration were significantly decreased (P < .05). α-Lipoic acid also reduced cell invasion through a Matrigel-coated chamber (P < .05). Activities of MMP-2 and MMP-9 were decreased by LA treatment in a dose-dependent manner. RT-PCR analysis confirmed the reduction in mRNA expression level of MMP-2 and MMP-9 by LA treatment. We conclude that in this cell culture model, LA treatment inhibits cancer metastasis, and this inhibition is likely due to the decrease in the activity and mRNA expression levels of MMP-2 and MMP-9 caused by LA.     

How are patient-reported outcomes and symptoms being measured in adults with relapsed/refractory multiple myeloma? A systematic review

Quality of Life Research - Patients with relapsed and/or refractory multiple myeloma (RRMM) are living longer due in part to changing treatment patterns. It is important to understand how changing...     

Induction of apoptotic cell death by phytoestrogens by up-regulating the levels of phospho-p53 and p21 in normal and malignant estrogen receptor α-negative breast cells

In this study, we investigated the underlying mechanism by which phytoestrogens suppress the growth of normal (MCF-10A) and malignant (MDA-MB-231) estrogen receptor α (ERα)-negative breast cells. We hypothesized that phytoestrogen inhibits the proliferation of ERα-negative breast cancer cells. We found that all tested phytoestrogens (genistein, apigenin, and quercetin) suppressed the growth of both MCF-10A and MDA-MB-231 cells, as revealed by proliferation assays. These results were accompanied by an increase in the sub-G0/G1 apoptotic fractions as well as an increase in the cell population in the G2/M phase in both cell types, as revealed by cell cycle analysis. When we assessed the effect of phytoestrogens on the level of intracellular signaling molecules by Western blot analysis, we found that phytoestrogens increased the level of active p53 (phospho-p53) without changing the p53 level in both MCF-10A and MDA-MB-231 cells. Phytoestrogens also induced an increase in p21, a p53 target gene, and a decrease in either Bcl-xL or cyclin B1 in both cell types. In contrast, the protein levels of phosphatase and tensin homolog, cyclin D1, cell division control protein 2 homolog, phospho-cell division control protein 2 homolog, and p27 were not changed after phytoestrogen treatment. Our data indicate that phytoestrogens induce apoptotic cell death of ERα-negative breast cancer cells via p53-dependent pathway and suggest that phytoestrogens may be promising agents in the treatment and prevention of ERα-negative breast cancer.     

Increased interleukin-10 but unchanged insulin sensitivity after 4 weeks of (1, 3)(1, 6)-β-glycan consumption in overweight humans

Obesity-induced insulin resistance has been suggested to be a systemic inflammatory condition with activation of the innate immune system. Animal studies indicate that certain dietary fibers such as (1,3)(1,6)-β-d-glycans (BDG) have potent effects on immune activity such as increasing the antiinflammatory cytokine interleukin-10 (IL-10) and reducing the secretion of inflammatory factors. Therefore, we hypothesized that BDG consumption improves inflammatory markers and insulin sensitivity in overweight and obese subjects with moderately increased levels of C-reactive protein, indicating subclinical inflammation. We screened 180 overweight and obese subjects for moderately increased C-reactive protein levels on 2 or more occasions, in the absence of any signs of acute infection. Twelve of the subjects met all inclusion criteria and were investigated in a randomized, double-blind, placebo-controlled, crossover design for 2 × 4 weeks (washout ≥4 weeks). Subjects ingested capsules containing 3 × 0.5 g of highly purified BDG or 3 × 0.5 g of placebo (waxy maize starch) daily. Maintenance of the normal diet of the participants and the correct intake of the capsules were monitored, using 6 × 3-day food recording and counting of the provided capsules. Predefined outcome measures were BDG-induced changes in pro and antiinflammatory markers in circulating blood and gene expression in adipose tissue and peripheral insulin sensitivity expressed as M value. The BDG consumption for 4 weeks significantly increased both circulating levels and adipose tissue messenger RNA (mRNA) expression of the antiinflammatory cytokine IL-10 in overweight and obese humans. Insulin sensitivity as well as circulating levels and mRNA expression of proinflammatory cytokines were unaffected by BDG treatment. Increased IL-10 after BDG consumption might be a contributing factor to the known beneficial effects of dietary fiber intake.     

Lysine α-ketoglutarate reductase, but not saccharopine dehydrogenase, is subject to substrate inhibition in pig liver

The activity of lysine α-ketoglutarate reductase (LKR), the initial enzyme in the principal pathway of lysine catabolism, is a primary determinant of whole-body lysine status. Past research indicated that LKR activity was predominantly hepatic; recent in vivo data suggest that other tissues can also catabolize lysine. The hypothesis of this investigation was that lysine catabolism takes place in extrahepatic tissues in pigs and that the enzymes involved may be subject to inhibition or activation. Using mitochondria from various tissues of market-age pigs, the activities of LKR and saccharopine dehydrogenase were measured. Liver mitochondria had the highest LKR activity, and the enzyme was subject to substrate inhibition. Mitochondria from the muscle, kidney, heart, and intestinal epithelial cells all had measurable LKR activity. The LKR activity was significantly inhibited by a variety of compounds including saccharopine, α-aminoadipate, α-ketoadipate, 5-hydroxy-l-lysine, and several metals. Oxidation of ¹⁴C-lysine to ¹⁴CO₂ was demonstrated in mitochondria isolated from the liver, muscle, and intestinal epithelial cells. Western blotting confirmed the presence of the α-aminoadipate δ-semialdehyde synthase protein in some extrahepatic tissues. These data show a significant capacity for lysine degradation in these extrahepatic tissues, most notably in cells of the intestine and muscle. These tissues should be considered important contributors to whole-body lysine catabolism.