Interindividual variability in response to protein and fish oil supplementation in older adults: a randomized controlled trial.

BACKGROUND: Precision nutrition is highly topical. However, no studies have explored the interindividual variability in response to nutrition interventions for sarcopenia. The purpose of this study was to determine the magnitude of interindividual variability in response to two nutrition supplementation interventions for sarcopenia and metabolic health, after accounting for sources of variability not attributable to supplementation. METHODS: A 24 week, randomized, double-blind, placebo-controlled trial tested the impact of leucine-enriched protein (LEU-PRO), LEU-PRO plus long-chain n-3 PUFA (LEU-PRO+n-3) or control (CON) supplementation in older adults (n = 83, 71 ± 6 years) at risk of sarcopenia. To estimate the true interindividual variability in response to supplementation (free of the variability due to measurement error and within-subject variation), the standard deviation of individual responses (SDR ) was computed and compared with the minimally clinically important difference (MCID) for appendicular lean mass (ALM), leg strength, timed up-and-go (TUG), and serum triacylglycerol (TG) concentration. Clinically meaningful interindividual variability in response to supplementation was deemed to be present when the SDR positively exceeded the MCID. The probability that individual responses were clinically meaningful, and the phenotypic, dietary, and behavioural determinants of response to supplementation were examined. RESULTS: The SDR was below the MCID for ALM (LEU-PRO: -0.12 kg [90% CI: -0.38, 0.35], LEU-PRO+n-3: -0.32 kg [-0.45, 0.03], MCID: 0.21 kg), TUG (LEU-PRO: 0.58 s [0.18, 0.80], LEU-PRO+n-3: 0.73 s [0.41, 0.95], MCID: 0.9 s) and TG (LEU-PRO: -0.38 mmol/L [-0.80, 0.25], LEU-PRO+n-3: -0.44 mmol/L [-0.63, 0.06], MCID: 0.1 mmol/L), indicating no meaningful interindividual variability in response to either supplement. The SDR exceeded the MCID (19 Nm) for strength in response to LEU-PRO (25 Nm [-29, 45]) and LEU-PRO+n-3 (23 Nm [-29, 43]) supplementation but the effect was uncertain, evidenced by wide confidence intervals. In the next stage of analysis, similar proportions of participant responses were identified as very likely, likely, possibly, unlikely, and very unlikely to represent clinically meaningful improvements across the LEU-PRO, LEU-PRO+n-3, and CON groups (P > 0.05). Baseline LC n-3 PUFA status, habitual protein intake, and numerous other phenotypic and behavioural factors were not determinants of response to LEU-PRO or LEU-PRO+n-3 supplementation. CONCLUSIONS: Applying a novel, robust methodological approach to precision nutrition, we show that there was minimal interindividual variability in changes in ALM, muscle function, and TG in response to LEU-PRO and LEU-PRO+n-3 supplementation in older adults at risk of sarcopenia.

Does supplementation with leucine-enriched protein alone and in combination with fish-oil-derived n-3 PUFA affect muscle mass, strength, physical performance, and muscle protein synthesis in well-nourished older adults? A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Leucine-enriched protein (LEU-PRO) and long-chain (LC) n-3 (ω-3) PUFAs have each been proposed to improve muscle mass and function in older adults, whereas their combination may be more effective than either alone. OBJECTIVE: The impact of LEU-PRO supplementation alone and combined with LC n-3 PUFAs on appendicular lean mass, strength, physical performance and myofibrillar protein synthesis (MyoPS) was investigated in older adults at risk of sarcopenia. METHODS: This 24-wk, 3-arm parallel, randomized, double-blind, placebo-controlled trial was conducted in 107 men and women aged ≥65 y with low muscle mass and/or strength. Twice daily, participants consumed a supplement containing either LEU-PRO (3 g leucine, 10 g protein; n = 38), LEU-PRO plus LC n-3 PUFAs (0.8 g EPA, 1.1 g DHA; LEU-PRO+n-3; n = 38), or an isoenergetic control (CON; n = 31). Appendicular lean mass, handgrip strength, leg strength, physical performance, and circulating metabolic and renal function markers were measured pre-, mid-, and postintervention. Integrated rates of MyoPS were assessed in a subcohort (n = 28). RESULTS: Neither LEU-PRO nor LEU-PRO+n-3 supplementation affected appendicular lean mass, handgrip strength, knee extension strength, physical performance or MyoPS. However, isometric knee flexion peak torque (treatment effect: -7.1 Nm; 95% CI: -12.5, -1.8 Nm; P < 0.01) was lower postsupplementation in LEU-PRO+n-3 compared with CON. Serum triacylglycerol and total adiponectin concentrations were lower, and HOMA-IR was higher, in LEU-PRO+n-3 compared with CON postsupplementation (all P < 0.05). Estimated glomerular filtration rate was higher and cystatin c was lower in LEU-PRO and LEU-PRO+n-3 postsupplementation compared with CON (all P < 0.05). CONCLUSIONS: Contrary to our hypothesis, we did not observe a beneficial effect of LEU-PRO supplementation alone or combined with LC n-3 PUFA supplementation on appendicular lean mass, strength, physical performance or MyoPS in older adults at risk of sarcopenia. This trial was registered at clinicaltrials.gov as NCT03429491.

The Impact of Protein Supplementation on Appetite and Energy Intake in Healthy Older Adults: A Systematic Review with Meta-Analysis.

Protein supplementation is an attractive strategy to prevent loss of muscle mass in older adults. However, it could be counterproductive due to adverse effects on appetite. This systematic review and meta-analysis aimed to determine the effects of protein supplementation on appetite and/or energy intake (EI) in healthy older adults. MEDLINE, The Cochrane Library, CINAHL, and Web of Science were searched up to June 2020. Acute and longitudinal studies in healthy adults ≥60 y of age that reported effects of protein supplementation (through supplements or whole foods) compared with control and/or preintervention (for longitudinal studies) on appetite ratings, appetite-related peptides, and/or EI were included. Random-effects model meta-analysis was performed on EI, with other outcomes qualitatively reviewed. Twenty-two studies (9 acute, 13 longitudinal) were included, involving 857 participants (331 males, 526 females). In acute studies (n = 8), appetite ratings were suppressed in 7 out of 24 protein arms. For acute studies reporting EI (n = 7, n = 22 protein arms), test meal EI was reduced following protein preload compared with control [mean difference (MD): -164 kJ; 95% CI: -299, -29 kJ; P  = 0.02]. However, when energy content of the supplement was accounted for, total EI was greater with protein compared with control (MD: 649 kJ; 95% CI: 438, 861 kJ; P < 0.00001). Longitudinal studies (n = 12 protein arms) showed a higher protein intake (MD: 0.29 g ⋅ kg-1 ⋅ d-1; 95% CI: 0.14, 0.45 g ⋅ kg-1 ⋅ d-1; P < 0.001) and no difference in daily EI between protein and control groups at the end of trials (MD: -54 kJ/d; 95% CI: -300, 193 kJ/d; P  = 0.67). While appetite ratings may be suppressed with acute protein supplementation, there is either a positive effect or no effect on total EI in acute and longitudinal studies, respectively. Therefore, protein supplementation may represent an effective solution to increase protein intakes in healthy older adults without compromising EI through appetite suppression. This trial was registered at PROSPERO as https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019125771 (CRD42019125771).

Conjugated Linoleic Acid and Alpha Linolenic Acid Improve Cholesterol Homeostasis in Obesity by Modulating Distinct Hepatic Protein Pathways.

SCOPE: High-fat diet (HFD)-induced obesity impairs macrophage-to-feces reverse cholesterol transport (RCT). It is hypothesized that dietary supplementation with the polyunsaturated fatty acids conjugated linoleic acid (CLA) or alpha linolenic acid (ALA) would prevent HFD-impaired RCT by modulating hepatic protein pathways. METHODS AND RESULTS: ApoE3L.CETP mice are fed a HFD supplemented ± CLA or ALA for 12 weeks and in vivo macrophage-to-feces RCT is determined. Hepatic cholesterol transporters and the hepatic proteome are assessed by immunoblotting and mass spectrometry, respectively. Mice fed HFD alone, but not ALA-HFD or CLA-HFD, exhibit increased systemic cholesterol levels, increased 3 H-cholesterol levels in plasma and liver but not feces during RCT, and reduced hepatic ABCG5/8 expression relative to LFD. ALA-HFD significantly reduces liver weight, hepatic cholesterol levels, and expression of the cholesterol synthesis enzyme farnesyl pyrophosphate synthase relative to HFD. ALA further increases the expression of acetyl-coA oxidase-associated proteins and suppress PPARα-induced proteins relative to HFD. CLA does not significantly attenuate hepatic lipid levels but is associated with reduced hepatic expression of fatty acid binding protein (FABP)-1/FABP4 levels relative to HFD, and reduced inflammatory pathway activation relative to ALA-HFD. CONCLUSION: ALA and CLA exert distinct mechanistic advantages on cholesterol homeostasis and RCT in obesity.

Dietary fat composition: replacement of saturated fatty acids with PUFA as a public health strategy, with an emphasis on α-linolenic acid.

SFA intakes have decreased in recent years, both in Ireland and across other European countries; however a large proportion of the population are still not meeting the SFA recommendation of <10% of total energy (TE). High SFA intakes have been associated with increased CVD and type-2 diabetes (T2D) risk, due to alterations in cholesterol homoeostasis and adipose tissue inflammation. PUFA, in particular EPA and DHA, have been associated with health benefits, including anti-inflammatory effects. It is well established that dietary fat composition plays an important role in biological processes. A recent review of evidence suggests that replacement of SFA with PUFA has potential to reduce risk of CVD and T2D. The public health and molecular impact of EPA and DHA have been well-characterised, while less is known of effects of α-linolenic acid (ALA). The current dietary guideline for ALA is 0·5% TE; however evidence from supplementation trials suggests that benefit is observed at levels greater than 2 g/d (0·6-1% TE). This review highlights the gap in the evidence base relating to effects of the replacement of SFA with ALA, identifying the need for randomised controlled trials to determine the optimal dose of ALA substitution to define the efficacy of dietary fat modification with ALA.

Personalized Cardio-Metabolic Responses to an Anti-Inflammatory Nutrition Intervention in Obese Adolescents: A Randomized Controlled Crossover Trial.

SCOPE: Chronic inflammation and hypoadiponectinemia are characteristics of obesity-induced insulin resistance (IR). The effect of an anti-inflammatory nutrition supplement (AINS) on IR and adiponectin biology in overweight adolescents was investigated. The secondary objective was to examine the extent to which individuals' biomarker profiles, derived from baseline phenotypes, predicted response or not to the AINS. Additionally, the impact of DNA methylation on intervention efficacy was assessed. METHODS AND RESULTS: Seventy overweight adolescents (13-18 years) were recruited to this randomized controlled crossover trial. Participants received an AINS (long chain n-3 PUFA, vitamin C, α-tocopherol, green tea extract, and lycopene) and placebo for 8 weeks each. Homeostatic model assessment (HOMA)-IR, adiponectin, inflammatory profiles, and DNA methylation were assessed. HOMA-IR was unchanged in the total cohort. High-molecular-weight (HMW) adiponectin was maintained following the AINS while it decreased over time following the placebo intervention. HOMA-IR decreased in 40% of subjects (responders) following the AINS. Responders' pretreatment phenotype was characterized by higher HOMA-IR, total and LDL cholesterol, but similar BMI in comparison to nonresponders. HMW adiponectin response to the AINS was associated with bidirectional modulation of adipogenic gene methylation. CONCLUSION: The AINS modulated adiponectin biology, an early predictor of type 2 diabetes risk, was associated with bidirectional modulation of adipogenic gene methylation in weight-stable overweight adolescents. HOMA-IR decreased in a sub-cohort of adolescents with an adverse metabolic phenotype. Thus, suggesting that more stratified or personalized nutrition approaches may enhance efficacy of dietary interventions.

Nutritional modulation of metabolic inflammation.

Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Peroxisome proliferator-activated receptors and AMP-activated protein kinase (AMPK) are regulators of cellular homeostasis that influence both inflammatory and metabolic pathways. Dietary fats, such as saturated fatty acids (SFAs), can differentially modulate metabolic inflammation. Palmitic acid, in particular, is a well-characterized nutrient that promotes metabolic inflammation via the NLRP3 (the nod-like receptor containing a pyrin domain) inflammasome, which is partly attributable to AMPK inhibition. Conversely, some unsaturated fatty acids are less potent agonists of metabolic inflammation. For example, monounsaturated fatty acid does not reduce AMPK as potently as SFA and n-3 polyunsaturated fatty acids actively resolve inflammation via resolvins and protectins. Nevertheless, the full extent to which nutritional state modulates metabolic inflammation requires greater clarification.

Impact of anti-inflammatory nutrients on obesity-associated metabolic-inflammation from childhood through to adulthood.

Obesity-related metabolic conditions such as insulin resistance (IR), type 2 diabetes and CVD share a number of pathological features, one of which is metabolic-inflammation. Metabolic-inflammation results from the infiltration of immune cells into the adipose tissue, driving a pro-inflammatory environment, which can induce IR. Furthermore, resolution of inflammation, an active process wherein the immune system counteracts pro-inflammatory states, may be dysregulated in obesity. Anti-inflammatory nutritional interventions have focused on attenuating this pro-inflammatory environment. Furthermore, with inherent variability among individuals, establishing at-risk populations who respond favourably to nutritional intervention strategies is important. This review will focus on chronic low-grade metabolic-inflammation, resolution of inflammation and the putative role anti-inflammatory nutrients have as a potential therapy. Finally, in the context of personalised nutrition, the approaches used in defining individuals who respond favourably to nutritional interventions will be highlighted. With increasing prevalence of obesity in younger people, age-dependent biological processes, preventative strategies and therapeutic options are important to help protect against development of obesity-associated co-morbidities.

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study.

BACKGROUND: Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. OBJECTIVE: Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. DESIGN: In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. RESULTS: Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). CONCLUSIONS: Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.

Proteome from patients with metabolic syndrome is regulated by quantity and quality of dietary lipids.

BACKGROUND: Metabolic syndrome is a multi-component disorder associated to a high risk of cardiovascular disease. Its etiology is the result of a complex interaction between genetic and environmental factors, including dietary habits. We aimed to identify the target proteins modulated by the long-term consumption of four diets differing in the quality and quantity of lipids in the whole proteome of peripheral blood mononuclear cells (PBMC). RESULTS: A randomized, controlled trial conducted within the LIPGENE study assigned 24 MetS patients for 12 weeks each to 1 of 4 diets: a) high-saturated fatty acid (HSFA), b) high-monounsaturated fatty acid (HMUFA), c) low-fat, high-complex carbohydrate diets supplemented with placebo (LFHCC) and d) low-fat, high-complex carbohydrate diets supplemented with long chain (LC) n-3 polyunsaturated fatty acids (PUFA) (LFHCC n-3). We analyzed the changes induced in the proteome of both nuclear and cytoplasmic fractions of PBMC using 2-D proteomic analysis. Sixty-seven proteins were differentially expressed after the long-term consumption of the four diets. The HSFA diet induced the expression of proteins responding to oxidative stress, degradation of ubiquitinated proteins and DNA repair. However, HMUFA, LFHCC and LFHCC n-3 diets down-regulated pro-inflammatory and oxidative stress-related proteins and DNA repairing proteins. CONCLUSION: The long-term consumption of HSFA, compared to HMUFA, LFHCC and LFHCC n-3, seems to increase the cardiovascular disease (CVD) risk factors associated with metabolic syndrome, such as inflammation and oxidative stress, and seem lead to DNA damage as a consequence of high oxidative stress.

Effects of the Mediterranean diet supplemented with coenzyme q10 on metabolomic profiles in elderly men and women.

BACKGROUND: Characterization of the variations in the metabolomic profiles of elderly people is a necessary step to understand changes associated with aging. This study assessed whether diets with different fat quality and supplementation with coenzyme Q10 (CoQ) affect the metabolomic profile in urine analyzed by proton nuclear magnetic resonance spectroscopy from elderly people. METHODS: Ten participants received, in a cross-over design, four isocaloric diets for 4-week periods each: Mediterranean diet supplemented with CoQ (Med + CoQ diet); Mediterranean diet; Western diet rich in saturated fat diet; low-fat, high-carbohydrate diet enriched in n-3 polyunsaturated fat. RESULTS: Multivariate analysis showed differences between diets when comparing Med + CoQ diet and saturated fat diet, with greater hippurate urine levels after Med + CoQ diet and higher phenylacetylglycine levels after saturated fat diet in women. Following consumption of Med + CoQ, hippurate excretion was positively correlated with CoQ and ß-carotene plasma levels and inversely related to Nrf2, thioredoxin, superoxide dismutase 1, and gp91(phox) subunit of NADPH oxidase gene expression. After saturated fat diet consumption, phenylacetylglycine excretion was inversely related to CoQ plasma level and positively correlated with isoprostanes urinary level. CONCLUSIONS: The association between hippurate excretion and antioxidant biomarkers along with the relationship between phenylacetylglycine excretion and oxidant biomarkers suggests that the long-term consumption of a Med + CoQ diet could be beneficial for healthy aging and a promising challenge in the prevention of processes related to chronic oxidative stress, such as cardiovascular and neurodegenerative disease.

Effect of dietary fat modification on subcutaneous white adipose tissue insulin sensitivity in patients with metabolic syndrome.

SCOPE: To determine whether the insulin resistance that exists in metabolic syndrome (MetS) patients is modulated by dietary fat composition. METHODS AND RESULTS: Seventy-five patients were randomly assigned to one of four diets for 12 wk: high-saturated fatty acids (HSFAs), high-MUFA (HMUFA), and two low-fat, high-complex carbohydrate (LFHCC) diets supplemented with long-chain n-3 (LFHCC n-3) PUFA or placebo. At the end of intervention, the LFHCC n-3 diet reduced plasma insulin, homeostasis model assessment of insulin resistance, and nonsterified fatty acid concentration (p < 0.05) as compared to baseline Spanish habitual (BSH) diet. Subcutaneous white adipose tissue (WAT) analysis revealed decreased EH-domain containing-2 mRNA levels and increased cbl-associated protein gene expression with the LFHCC n-3 compared to HSFA and HMUFA diets, respectively (p < 0.05). Moreover, the LFHCC n-3 decreased gene expression of glyceraldehyde-3-phosphate dehydrogenase with respect to HMUFA and BSH diets (p < 0.05). Finally, proteomic characterization of subcutaneous WAT identified three proteins of glucose metabolism downregulated by the LFHCC n-3 diet, including annexin A2. RT-PCR analysis confirmed the decrease of annexin A2 (p = 0.027) after this diet. CONCLUSION: Our data suggest that the LFHCC n-3 diet reduces systemic insulin resistance and improves insulin signaling in subcutaneous WAT of MetS patients compared to HSFA and BSH diets consumption.

Peripheral blood mononuclear cells as in vivo model for dietary intervention induced systemic oxidative stress.

Our aim was to assess the use of peripheral blood mononuclear cells (PBMC) as an in vivo cellular model to evaluate diet-induced changes in the oxidative stress status by analyzing the gene expression pattern of NADPH-oxidase subunits and antioxidant genes. A randomized, controlled trial assigned metabolic syndrome patients to 4 diets for 12 weeks each: (i) high-saturated fatty acid (HSFA), (ii) high-monounsaturated fatty acid, and (iii), (iv) two low-fat, high-complex carbohydrate diets supplemented with n-3 polyunsaturated fatty acids or placebo. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. The mRNA levels of gp91(phox) (P<0.001), p22(phox) (P=0.005), p47(phox) (P=0.001) and p40(phox) (P<0.001) increased at 2h after the intake of the HSFA meal. The expression of SOD1, SOD2, GSR, GPx1, GPX4, TXN, TXNRD1 and Nrf2 increased after the HSFA meal (p<0.05). In contrast, the expression of these genes remained unaltered in response to the other dietary interventions. Our results suggest that the increased expression of antioxidant genes in PBMC seems to be due to the response to the postprandial oxidative stress generated mainly in adipose tissue after the consumption of an HSFA diet.

Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota in C57BL/6J mice.

Macronutrient quality and composition are important determinants of energy balance and the gut microbiota. Here, we investigated how changes to protein quality (casein versus whey protein isolate; WPI) and the protein to carbohydrate (P/C) ratio within a high fat diet (HFD) impacts on these parameters. Mice were fed a low fat diet (10% kJ) or a high fat diet (HFD; 45% kJ) for 21 weeks with either casein (20% kJ, HFD) or WPI at 20%, 30% or 40% kJ. In comparison to casein, WPI at a similar energy content normalised energy intake, increased lean mass and caused a trend towards a reduction in fat mass (P = 0.08), but the protein challenge did not alter oxygen consumption or locomotor activity. WPI reduced HFD-induced plasma leptin and liver triacylglycerol, and partially attenuated the reduction in adipose FASN mRNA in HFD-fed mice. High throughput sequence-based analysis of faecal microbial populations revealed microbiota in the HFD-20% WPI group clustering closely with HFD controls, although WPI specifically increased Lactobacillaceae/Lactobacillus and decreased Clostridiaceae/Clostridium in HFD-fed mice. There was no effect of increasing the P/C ratio on energy intake, but the highest ratio reduced HFD-induced weight gain, fat mass and plasma triacylglycerol, non-esterified fatty acids, glucose and leptin levels, while it increased lean mass and oxygen consumption. Similar effects were observed on adipose mRNA expression, where the highest ratio reduced HFD-associated expression of UCP-2, TNFα and CD68 and increased the diet-associated expression of ß3-AR, LPL, IR, IRS-1 and GLUT4. The P/C ratio also impacted on gut microbiota, with populations in the 30/40% WPI groups clustering together and away from the 20% WPI group. Taken together, our data show that increasing the P/C ratio has a dramatic effect on energy balance and the composition of gut microbiota, which is distinct from that caused by changes to protein quality.

Dietary fat differentially influences the lipids storage on the adipose tissue in metabolic syndrome patients.

PURPOSE: Adipose tissue is now recognized as a highly active metabolic and endocrine organ. Our aim was to investigate the effect of the dietary fat on the two main adipose tissue functions, endocrine and lipid store, by analyzing the adipose tissue gene expression from metabolic syndrome patients. METHODS: A randomized, controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to 1 of 4 isoenergetic diets: (1) high-saturated fatty acid (HSFA), (2) high-monounsaturated fatty acid (HMUFA), (3) low-fat, high-complex carbohydrate diet supplemented with long-chain n-3 fatty acids (LFHCC n-3), and (4) low-fat, high-complex carbohydrate diet supplemented with placebo (LFHCC), for 12 weeks each. A fat challenge reflecting the fatty acid composition as the original diets was conducted post-intervention. RESULTS: The long-term consumption of HSFA, LFHCC, and LFHCC n-3 diets, but not HMUFA diet, decreased the perilipin fasting mRNA levels. LFHCC diet consumption increased fasting FABP4 expression, while it was reduced by the consumption of LFHCC n-3 diet. LFHCC meal reduced, while LFHCC n-3 meal intake increased postprandial CAV1 expression. CONCLUSION: The quantity and quality of dietary fat induce differential lipid storage and processing related gene expression, which may interact with the expression of adipokines through common regulatory mechanisms.

Diet and metabolic syndrome: an overview.

The metabolic syndrome (MetS) is a complex multifactorial disorder and its incidence is on the increase worldwide. Due to the definitive link between obesity and the MetS weight loss strategies are of prime importance in halting the spread of MetS. Numerous epidemiological studies provide evidence linking dietary patterns to incidence of MetS symptoms. As a consequence of the epidemiology studies, dietary intervention studies which analyse the effects of supplementing diets with particular nutrients of interest on the symptoms of the MetS have been conducted. Evidence has shown that lifestyle intervention comprising changes in dietary intake and physical activity leads to an improved metabolic profile both in the presence or absence of weight loss thus highlighting the importance of a multi-faceted approach in combating MetS. Nutritional therapy research is not focused solely on reducing energy intake and manipulating macronutrient intake but is investigating the role of functional foods or bioactive components of food. Such bioactives which target weight maintenance and /or insulin sensitivity may have a potentially positive effect on the symptoms of the MetS. However the efficacy of different functional nutrients needs to be further defined and clearly demonstrated.

Whey protein isolate counteracts the effects of a high-fat diet on energy intake and hypothalamic and adipose tissue expression of energy balance-related genes.

The intake of whey protein isolate (WPI) is known to reduce high-fat diet (HFD)-induced body-weight gain and adiposity. However, the molecular mechanisms are not fully understood. To this end, we fed C57BL/6J mice for 8 weeks with diets containing 10 % energy as fat (low-fat diet, LFD) or 45 % energy as fat (HFD) enriched with either 20 % energy as casein (LFD and HFD) or WPI (high-fat WPI). Metabolic parameters and the hypothalamic and epididymal adipose tissue expression of energy balance-related genes were investigated. The HFD increased fat mass and plasma leptin levels and decreased the dark-phase energy intake, meal number, RER, and metabolic (VO2 and heat) and locomotor activities compared with the LFD. The HFD increased the hypothalamic tissue mRNA expression of the leptin receptor, insulin receptor (INSR) and carnitine palmitoyltransferase 1b (CPT1b). The HFD also reduced the adipose tissue mRNA expression of GLUT4 and INSR. In contrast, WPI reduced fat mass, normalised dark-phase energy intake and increased meal size in HFD-fed mice. The dietary protein did not have an impact on plasma leptin, insulin, glucose or glucagon-like peptide 1 levels, but increased plasma TAG levels in HFD-fed mice. At a cellular level, WPI significantly reduced the HFD-associated increase in the hypothalamic tissue mRNA expression of the leptin receptor, INSR and CPT1b. Also, WPI prevented the HFD-induced reduction in the adipose tissue mRNA expression of INSR and GLUT4. In comparison with casein, the effects of WPI on energy intake and hypothalamic and adipose tissue gene expression may thus represent a state of reduced susceptibility to weight gain on a HFD.

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.

Impact of leucine on energy balance.

Body weight is determined by the balance between energy intake and energy expenditure. When energy intake exceeds energy expenditure, the surplus energy is stored as fat in the adipose tissue, which causes its expansion and may even lead to the development of obesity. Thus, there is a growing interest to develop dietary interventions that could reduce the current obesity epidemic. In this regard, data from a number of in vivo and in vitro studies suggest that the branched-chain amino acid leucine influences energy balance. However, this has not been consistently reported. Here, we review the literature related to the effects of leucine on energy intake, energy expenditure and lipid metabolism as well as its effects on the cellular activity in the brain (hypothalamus) and in peripheral tissues (gastro-intestinal tract, adipose tissue, liver and muscle) regulating the above physiological processes. Moreover, we discuss how obesity may influence the actions of this amino acid.

Postprandial changes in the proteome are modulated by dietary fat in patients with metabolic syndrome.

Metabolic syndrome is a multicomponent disorder whose etiology is the result of a complex interaction between genetic, metabolic and environmental factors including dietary habits. Our aim was to identify proteome-diet interactions during the postprandial state after the acute intake of four meals with different qualities of fat in the proteome of peripheral blood mononuclear cells. A randomized controlled trial conducted within the LIPGENE study assigned 39 metabolic syndrome patients to one of four meals: a high-saturated-fatty-acid (HSFA) meal, a high-monounsaturated-fatty-acid (HMUFA) meal and two high-polyunsaturated-fatty-acid (from walnut) (HPUFA) meals supplemented with n-3 PUFA or placebo. We analyzed the postprandial changes in the whole proteome of both nuclear and cytoplasmic fractions of peripheral blood mononuclear cells by two-dimensional proteomics. Twenty-three proteins were differentially expressed. HSFA intake caused the postprandial increase of proteins responding to oxidative stress (HSPA1A, PDIA3 and PSME1) and DNA damage (SMC6), whereas HMUFA intake led to the up-regulation of HSPA1A and PDIA3. HPUFA meal supplementation with n-3 PUFA produced peroxisomal beta-oxidation inhibition by down-regulation of ECH1, a process related to insulin signaling improvement. In conclusion, HSFA meal intake causes deleterious postprandial changes in the proteome in terms of DNA damage and procoagulant state, which reflect a higher postprandial oxidative stress after HSFA meal intake as compared to intake of HMUFA and HPUFA meals. Moreover, the addition of long-chain n-3 PUFA to an HPUFA meal may improve insulin signaling and exerts an anti-inflammatory effect when compared to an HPUFA meal.