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1.
Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial.
Costabile, G, Della Pepa, G, Salamone, D, Luongo, D, Naviglio, D, Brancato, V, Cavaliere, C, Salvatore, M, Cipriano, P, Vitale, M, et al
Nutrients. 2022;(10)
Abstract
BACKGROUND Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or β-oxidation. METHODS According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. RESULTS Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). CONCLUSIONS A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.
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2.
An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial.
Della Pepa, G, Brancato, V, Costabile, G, Salamone, D, Corrado, A, Vitale, M, Cavaliere, C, Mancini, M, Salvatore, M, Luongo, D, et al
Diabetes care. 2022;(9):1935-1942
Abstract
OBJECTIVE To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. RESULTS After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023). CONCLUSIONS In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.
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3.
Acute and chronic improvement in postprandial glucose metabolism by a diet resembling the traditional Mediterranean dietary pattern: Can SCFAs play a role?
Vitale, M, Giacco, R, Laiola, M, Della Pepa, G, Luongo, D, Mangione, A, Salamone, D, Vitaglione, P, Ercolini, D, Rivellese, AA
Clinical nutrition (Edinburgh, Scotland). 2021;(2):428-437
Abstract
BACKGROUND & AIMS Postprandial metabolic abnormalities are considered important and independent risk factors for cardiovascular diseases. However, the effects of the Mediterranean diet on postprandial metabolism and the mechanism underpinning the effects on clinical variables have not been exhaustively explored. Therefore, the aims of the present study were to evaluate the acute and medium-term effects (8 weeks) on postprandial glucose and lipid metabolism of a diet resembling a typical Mediterranean diet (Med-D) compared to a western-type diet (Control-D), and the mechanisms underlying those effects. METHODS Twenty-nine overweight/obese individuals of both genders, aged 20-60 years, were enrolled and randomly assigned to two isoenergetic dietary interventions: 1) a Med-D (n = 16), and 2) a Control-D (n = 13). Adherence to the dietary interventions was assessed by a 7-day food record. A meal test resembling the assigned diet was performed at baseline and after 8 weeks of intervention. Blood samples at fasting and over 4-h after the meal were collected to assess metabolic parameters and short chain fatty acid (SCFA) levels. Fecal samples were also collected to evaluate the microbiota composition. RESULTS Glucose and insulin responses were significantly reduced at baseline after the Med test meal compared to the Control meal (p < 0.05) and this effect was strengthened after 8 weeks of intervention with the Mediterranean diet (p < 0.05); together with an improvement in OGIS. At the end of the intervention, postprandial plasma butyric acid incremental area under the curve (IAUC) was significantly increased in the Med-D group (p = 0.019) and correlated inversely with plasma insulin IAUC and directly with oral glucose insulin sensitivity (OGIS) (r: -0.411, p = 0.046 and r: 0.397, p = 0.050 respectively). These metabolic changes were accompanied by significant changes in gut microbiota, such as an increase in the relative abundance of Intestinimonas butyriciproducens and Akkermansia muciniphila (p < 0.05) in the Med-D compared to Control-D group. CONCLUSIONS Our study provides strong evidence that a diet resembling the traditional Med-D improves postprandial glucose metabolism and insulin sensitivity. Furthermore, the study highlights a possible involvement of gut microbiota metabolites - such as butyric acid, and of dietary fiber as a precursor - in improving glucose metabolism and insulin sensitivity.
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4.
Nutritional factors influencing plasma adiponectin levels: results from a randomised controlled study with whole-grain cereals.
Polito, R, Costabile, G, Nigro, E, Giacco, R, Vetrani, C, Anniballi, G, Luongo, D, Riccardi, G, Daniele, A, Annuzzi, G
International journal of food sciences and nutrition. 2020;(4):509-515
Abstract
Data from intervention studies about the effects of a high intake of whole-grain cereals on adiponectin expression are still inconclusive. We evaluated the effects of whole-grain or refined cereals on fasting and postprandial serum adiponectin in people at high cardiovascular risk. According to a randomised controlled parallel group design, participants with metabolic syndrome were assigned to an isoenergetic diet based on either whole-grain cereal (WGC) or refined cereal (RC) products for 12-weeks. Anthropometric and biochemical measures were taken. Compared to baseline, fasting and postprandial serum adiponectin levels increased after both RC and WGC. In the WGC and RC groups combined, adiponectin concentrations significantly increased after 12-week intervention, and are directly associated with plasma SCFAs and acetate. Only increasing whole-grain cereals may not influence adiponectin levels, which could be modified by a fibre rich, low-fat, low-glycemic index diet, possibly through changes in gut microbiota, as suggested by the relation with SCFAs.Clinical Trials number: NCT00945854.
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5.
Microbial transglutaminase: A biotechnological tool to manage gluten intolerance.
Luongo, D, Maurano, F, Bergamo, P, Rossi, M
Analytical biochemistry. 2020;:113584
Abstract
Celiac disease (CD) is a chronic immune-mediated disease in which gluten ingestion leads to damage of the small intestinal mucosa in genetically susceptible individuals. The enteropathy is mainly induced by the production of IFN-γ from intestinal CD4+T cells that recognise gliadin peptides following deamidation by tissue transglutaminase. The only available therapy is a strict, lifelong gluten-free diet (GFD). This diet is strongly demanding for patients, which justifies the search for alternative strategies. The enzyme approach is one promising strategy to address this issue. In particular, transamidation of wheat gliadin by microbial transglutaminase (mTG) was fully effective at inhibiting gliadin-specific IFN-γ secretion in intestinal T cells from CD patients. Furthermore, transamidated gliadin induced higher levels of the anti-inflammatory IL-10 than native gliadin in different in vitro models. These data suggest that a more balanced immune response could be induced by mTG-treated gliadin in the small intestine of celiac patients. Furthermore, the highlighted biological property of mTG-treated gliadin could be exploited to induce tolerance to native gliadin in at-risk individuals.
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6.
Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.
Costabile, G, Vitale, M, Luongo, D, Naviglio, D, Vetrani, C, Ciciola, P, Tura, A, Castello, F, Mena, P, Del Rio, D, et al
Clinical nutrition (Edinburgh, Scotland). 2019;(6):2727-2734
Abstract
BACKGROUND & AIMS Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER NCT02865278.
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7.
Modulation of the cytokine profile in Caco-2 cells by faecal lactobacilli and bifidobacteria from individuals with distinct dietary habits.
Luongo, D, Coppola, A, Treppiccione, L, Bergamo, P, Sorrentino, A, Ferrocino, I, Turroni, S, Neviani, E, Di Cagno, R, Cocolin, L, et al
Cytokine. 2017;:80-87
Abstract
Enterocytes are actively involved in the defense against pathogens and they limit penetration of commensal microbes into tissues. They also have an important role in gut immunity as enterocytes confer mucosal dendritic cell specialisation. On the other hand, the microbiota is directly involved in the development and modulation of the intestinal immune system. Particularly, lactobacilli and bifidobacteria play a primary role in shaping the immune response. We further explored this issue by evaluating whether functional differences in Caco-2 cells could characterise faecal populations of lactobacilli (155 samples) and bifidobacteria (110 samples) isolated from three dietary cohorts (omnivores, ovo-lacto-vegetarians and vegans) recruited at four Italian centres (Turin, Parma, Bologna and Bari). According to our findings, tested bacteria were unable to modulate expression of IL-8, IL-10, TGF-β or thymic stromal lymphopoietin (TSLP) cytokines in unstimulated Caco-2 cells. Conversely, in phorbol 12-myristate 13-acetate and ionomycin (PMA/Io) stimulated Caco-2 cells, lactobacilli from the omnivorous group and all bifidobacteria significantly down-regulated IL-8. Notably, both genera also lowered the TSLP expression in stimulated Caco-2 cells, regardless of the diet regimen. By further examining these data on the basis of geographical origin, we found that lactobacilli from the vegetarian group recruited in Bari, significantly up-regulated this cytokine. In conclusion, we highlighted a peculiar immune-modulatory activity profile for lactobacilli on enterocytes undergoing a stimulatory signal, which was associated with a specific dietary habit. Furthermore, the geographical area had a significant impact on the inflammatory potential of members of the Lactobacillus genus.
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8.
Reduction in liver fat by dietary MUFA in type 2 diabetes is helped by enhanced hepatic fat oxidation.
Bozzetto, L, Costabile, G, Luongo, D, Naviglio, D, Cicala, V, Piantadosi, C, Patti, L, Cipriano, P, Annuzzi, G, Rivellese, AA
Diabetologia. 2016;(12):2697-2701
Abstract
AIMS/HYPOTHESIS The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs). METHODS This is an ancillary analysis of a published study. In a parallel-group design, 30 men and eight women, aged 35-70 years, with type 2 diabetes and whose blood glucose was controlled satisfactorily (HbA1c < 7.5% [58 mmol/mol]) by diet or diet plus metformin, were randomised by MINIM software to follow either a high-carbohydrate/high-fibre/low-glycaemic index diet (CHO/fibre diet, n = 20) or a high-MUFA diet (MUFA diet, n = 18) for 8 weeks. The assigned diets were known for the participants and blinded for people doing measurements. Before and after intervention, LF was measured by 1H-MRS (primary outcome) and indirect indices of de novo lipogenesis (DNL) (serum triacylglycerol palmitic:linoleic acid ratio), stearoyl-CoA desaturase activity (SCD-1) (serum triacylglycerol palmitoleic:palmitic acid ratio) and hepatic β-oxidation of fatty acids (β-hydroxybutyrate plasma concentrations) were measured. RESULTS LF was reduced by 30% after the MUFA diet, as already reported. Postprandial β-hydroxybutyrate incremental AUC (iAUC) was significantly less suppressed after the MUFA diet (n = 16) (-2504 ± 4488 μmol/l × 360 min vs baseline -9021 ± 6489 μmol/l × 360 min) while it was unchanged after the CHO/fibre diet (n = 17) (-8168 ± 9827 μmol/l × 360 min vs baseline -7206 ± 10,005 μmol/l × 360 min, p = 0.962) (mean ± SD, p = 0.043). In the participants assigned to the MUFA diet, the change in postprandial β-hydroxybutyrate iAUC was inversely associated with the change in LF (r = -0.642, p = 0.010). DNL and SCD-1 indirect indices did not change significantly after either of the dietary interventions. CONCLUSIONS/INTERPRETATION Postprandial hepatic oxidation of fatty acids is a metabolic process possibly involved in the reduction of LF by a MUFA-rich diet in patients with type 2 diabetes. TRIAL REGISTRATION ClinicalTrials.gov NCT01025856 FUNDING The study was funded by Ministero Istruzione Università e Ricerca and Italian Minister of Health.
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9.
Effects of whole-grain cereal foods on plasma short chain fatty acid concentrations in individuals with the metabolic syndrome.
Vetrani, C, Costabile, G, Luongo, D, Naviglio, D, Rivellese, AA, Riccardi, G, Giacco, R
Nutrition (Burbank, Los Angeles County, Calif.). 2016;(2):217-21
Abstract
OBJECTIVE Short chain fatty acids (SCFAs) derived from dietary fiber fermentation by gut microbiota have been identified as one of the mechanisms behind the association between habitual whole-grain intake and a lower risk of cardiometabolic diseases. The aims of the present work are: (1) to evaluate whether a whole-grain wheat-based diet may increase SCFAs concentration, and (2) to identify possible associations between SCFAs and metabolic changes observed after the nutritional intervention. METHODS Fifty-four subjects participated in the trial. They underwent a 12-wk dietary intervention based on whole-grain or refined cereal products. At baseline and after the intervention, glucose, insulin, triacylglycerol, inflammatory markers (hs-CRP, IL-1 ra, IL-6, and TNF-α), and SCFAs plasma concentrations were evaluated. RESULTS After the intervention, in the whole-grain group fasting plasma propionate concentrations were higher than at baseline, whereas a reduction was detected in the control group. The absolute changes (end of trial minus baseline) in fasting plasma propionate concentrations were significantly different between the two groups (P = 0.048). The absolute changes of fasting propionate correlated with cereal fiber intake (r = 0.358, P = 0.023), but no significant correlations with clinical outcomes were found. However, postprandial insulin was significantly decreased in the group having the absolute changes of fasting propionate concentration above the median value (P = 0.022 versus subjects with fasting propionate changes below the median value). CONCLUSIONS A 12-wk whole-grain wheat-based diet increases fasting plasma propionate. This increase correlates with the cereal fiber intake and is associated with lower postprandial insulin concentrations.
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10.
Trans fatty acids consumption in type 1 diabetic patients: evaluation by dietary records and measurement in serum phospholipids.
Vitale, M, Luongo, D, Naviglio, D, Bozzetto, L, Mirabella, M, Rivieccio, AM, Giacco, A, Rivellese, AA
Acta diabetologica. 2013;(4):651-4
Abstract
The consumption of foods containing trans fatty acids (TFA), especially those produced by food industries, induces pleiotropic negative effects on health. Therefore, it is important to assess the amount of TFA consumed, especially in age groups more exposed to the consumption of TFA-containing foods. The present pilot study evaluates TFA intake in 54 young people with and without type 1 diabetes (29 young subjects with type 1 diabetes and 25 healthy subjects) through both dietary records (7-day food record) and the measurement of TFA levels in serum phospholipids, a possibly more objective marker of TFA intake. The comparison between the two groups was made by the student t test for independent samples. The intake of synthetic TFA was low in both groups (type 1 diabetic patients: 0.25 ± 0.25 g/day; healthy subjects 0.48 ± 0.37 g/day), but significantly lower in diabetic patients vs controls (P < 0.05); TFA levels in serum phospholipids also confirmed a low intake of these fatty acids. These data indicate that the intake of trans fatty acids is relatively low in our population, i.e.,<1% of total calories in the diet, in line with what recommended by the World Health Organization.