Anika Nier

Purpose: The consumption of highly processed food is often associated with a high intake of inorganic phosphate. Hyperphosphatemia is accompanied by an inflammatory status in patients with chronic kidney disease. However, the immune response to high phosphorus intake in healthy individuals is largely unknown. Therefore, the aim of the present study was to evaluate the effect of a single phosphate-enriched meal on inflammasome activity and plasma levels of inflammatory markers. Methods: The analysis included 28 participants who received a single dose of either 700 mg phosphorus or a placebo with a test meal. At baseline, 4 and 8 h post-meal, plasma interleukin (IL)-6, IL-1β, IL-10, c-reactive protein (CRP), soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (sgp130) levels were determined. At baseline and 4 h post-meal, peripheral blood mononuclear cells were isolated to assess inflammasome activity. Subsequently, the effect of phosphate with or without glucose on IL-6 and IL-1β gene expression and secretion in U937 monocytes was examined. Results: While both groups showed a marked postprandial increase in IL-6 plasma levels, neither plasma levels of IL-6, IL-1β, CRP, IL-10, sIL-6R, and sgp130 nor inflammasome activity were affected by phosphate compared to placebo. In U937 cells, there was also no effect of phosphate on IL-6 expression, but the addition of glucose increased it. Phosphate, however, reduced the IL-1β secretion of these cells. Conclusion: Postprandial inflammatory markers were not affected by dietary phosphate. However, IL-6 plasma levels were markedly increased post-meal, which appears to be a metabolic rather than a pro-inflammatory phenomenon. Trial registration number: ClinicalTrials.gov, NCT03771924, date of registration: 11th December 2018, retrospectively registered.

The addition of plant oils such as soybean oil (S) to a diet rich in saturated fatty acids is discussed as a possible route to prevent or diminish the development of metabolic disease. Here, we assessed whether a butterfat-rich diet fortified with S affects the development of early non-alcoholic steatohepatitis (NASH) and glucose intolerance. Female C57BL/6J mice were fed a standard-control diet (C); a fat-, fructose-, and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt./wt.) fructose, 0.16% (wt./wt.) cholesterol); or FFC supplemented with S (FFC + S, 21E% butterfat + 4E% S) for 13 weeks. Indicators of liver damage, inflammation, intestinal barrier function, and glucose metabolism were measured. Lipopolysaccharide (LPS)-challenged J774A.1 cells were incubated with linolenic and linoleic acids (ratio 1:7.1, equivalent to S). The development of early NASH and glucose intolerance was significantly attenuated in FFC + S–fed mice compared to FFC-fed mice associated with lower hepatic toll-like receptor-4 mRNA expression, while markers of intestinal barrier function were significantly higher than in C-fed mice. Linolenic and linoleic acid significantly attenuated LPS-induced formation of reactive nitrogen species and interleukin-1 beta mRNA expression in J774A.1 cells. Our results indicate that fortifying butterfat with S may attenuate the development of NASH and glucose intolerance in mice.

Sodium butyrate (SoB) supplementation has been suggested to attenuate the development of non-alcoholic fatty liver disease (NAFLD). Here, we determined the therapeutic potential of SoB on NAFLD progression and molecular mechanism involved. Eight-week old C57BL/6J mice were pair-fed a fat-, fructose- and cholesterol-rich diet (FFC) or control diet (C). After 8 weeks, some mice received 0.6g SoB/kg bw in their respective diets (C+SoB; FFC+SoB) or were maintained on C or FFC for the next 5 weeks of feeding. Liver damage, markers of glucose metabolism, inflammation, intestinal barrier function and melatonin metabolism were determined. FFC-fed mice progressed from simple steatosis to early non-alcoholic steatohepatitis, along with significantly higher TNFα and IL-6 protein levels in the liver and impaired glucose tolerance. In FFC+SoB-fed mice, disease was limited to steatosis associated with protection against the induction of Tlr4 mRNA and iNOS protein levels in livers. SoB supplementation had no effect on FFC-induced loss of tight junction proteins in the small intestine but was associated with protection against alterations in melatonin synthesis and receptor expression in the small intestine and livers of FFC-fed animals. Our results suggest that the oral supplementation of SoB may attenuate the progression of simple steatosis to steatohepatitis.

(1) Background: The etiology of non-alcoholic fatty liver disease (NAFLD) is multifactorial. Dietary composition has been implicated as a factor modulating intestinal barrier and could affect disease severity. The aim of this study was to evaluate dietary intake and markers of intestinal permeability in patients with NAFLD. (2) Methods: We enrolled 63 patients with NAFLD and compared them to age-matched controls. (3) Results: body mass index (BMI) and leptin to adiponectin ratio—the latter being an indicator of abdominal fat accumulation—correlated with the degree of hepatic steatosis being accompanied with rising levels of fasting insulin. Furthermore, endotoxin plasma levels and markers of inflammation were significantly higher in NAFLD compared to controls and increased with the severity of hepatic steatosis. Despite comparable intake of total energy and macronutrients, intake of fiber was lower in all patients with NAFLD compared to controls and were negatively related to disease severity. (4) Conclusions: Taken together, results of the present study suggest that fiber intake in patients is negatively related to steatosis degree and bacterial endotoxin levels, further suggesting that dietary fiber intake may be a target in NAFLD treatment (NCT: 02366052 and 03482284).

Being overweight has been identified as the main risk factor for the development of metabolic disorders in adults and children. However, recent studies suggest that normal weight individuals are also frequently affected by metabolic abnormalities with underlying mechanisms not yet fully understood. The aim of the present study was to determine if dietary pattern and markers of intestinal permeability, as well as inflammation, differ between normal weight healthy children and normal weight children suffering from metabolic abnormalities. In total, 45 normal weight children aged 5–9 years were included in the study, of whom nine suffered from metabolic abnormalities. Anthropometric data, dietary intake and markers of inflammation, as well as intestinal permeability, were assessed in fasting blood samples. Neither BMI nor BMI-SDS differed between groups; however, children with metabolic abnormalities had a significantly larger waist circumference (+~5 cm) and a higher leptin to adiponectin ratio. While plasma leptin levels are significantly higher in normal weight children with metabolic abnormalities, neither TNF α nor sCD14, adiponectin, PAI-1 or IL-6 plasma levels differed between groups. Despite similar total calorie and macronutrient intake between groups, mean total fructose and total glucose intake (resulting mainly from sugar sweetened beverages, fruits and sweets) were higher in children with metabolic abnormalities than in healthy children. Time spent physically active was significantly higher in healthy normal weight children whereas time spent physically inactive was similar between groups. Furthermore, bacterial endotoxin levels were significantly higher in the peripheral plasma of normal weight children with metabolic abnormalities than in healthy normal weight children. Our results suggest that metabolic disorders in normal weight children are associated with a high monosaccharide intake and elevated bacterial endotoxin as well as leptin plasma levels, the latter also discussed as being indicative of visceral adiposity.

The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children (n = 89, aged 5–9) and normal-weight healthy controls (n = 36, aged 5–9). Sixteen children suffered from early signs of NAFLD, e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing early signs of NAFLD were enrolled in the intervention study (n = 6 intervention, n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS), and waist circumference were significantly higher in NAFLD children than in overweight children without NAFLD. Levels of bacterial endotoxin, lipopolysaccharide-binding protein (LBP), and proinflammatory markers like interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were also significantly higher in overweight children with NAFLD compared to those without. Total energy and carbohydrate intake were higher in NAFLD children than in those without. The higher carbohydrate intake mainly resulted from a higher total fructose and glucose intake derived from a significantly higher consumption of sugar-sweetened beverages. When counseling children with NAFLD regarding fructose intake (four times, 30–60 min within 1 year; one one-on-one counseling and three group counselings), neither alanine aminotransferase (ALT) nor aspartate aminotransferase (AST) activity in serum changed; however, diastolic blood pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly in the intervention group after one year. Similar changes were not found in uncounseled children. Our results suggest that a sugar-rich diet might contribute to the development of early stages of NAFLD in overweight children, and that moderate dietary counseling might improve the metabolic status of overweight children with NAFLD.

Sowohl bei Erwachsenen als auch bei Kindern und Jugendlichen ist die Prävalenz von Übergewicht und Adipositas und damit assoziierten Erkrankungen wie Bluthochdruck, Insulinresistenz und nicht-alkoholbedingte Fettlebererkrankung in den letzten Jahrzehnten weltweit deutlich gestiegen. Trotz intensiver Bemühungen sind die Mechanismen, die der Entstehung dieser Adipositas-assoziierten Erkrankungen zugrunde liegen, bislang nicht eindeutig geklärt. Epidemiologische und tierexperimentelle Studien, aber auch Interventionsstudien beim Menschen weisen darauf hin, dass neben einer generellen Überernährung und genetischen Prädispositionen auch eine erhöhte Aufnahme von bestimmten Makronährstoffen wie Fruktose in diesem Kontext von Bedeutung ist. Im vorliegenden Übersichtsartikel werden aktuelle Daten zur Untersuchung des Zusammenhangs von erhöhter Fruktoseaufnahme und Entstehung metabolischer Erkrankungen zusammengefasst. Die Literatur finden Sie online unter www. adipositas-journal.de During the last decades, the prevalence of overweight and obesity and related diseases like hypertension, insulin resistance and nonalcoholic fatty liver disease has increased dramatically among adults, children and adolescents worldwide. Despite intense efforts, mechanisms involved in the development of overweight-associated diseases are not yet fully understood. Results of epidemiological and animal studies but also human intervention studies suggest that besides overnutrition and genetic predispositions, an elevated intake of certain macronutrients like fructose may be critical in this context. Results of recent studies assessing the effect of elevated fructose intake and the development of metabolic diseases are summarized in this review article.