Margrit Kemper

WISP1 Is a Novel Adipokine Linked to Inflammation in Obesity

WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the secreted extracellular matrix–associated proteins of the CCN family and a target gene of the Wingless-type (WNT) signaling pathway. Growing evidence links the WNT signaling pathway to the regulation of adipogenesis and low-grade inflammation in obesity. We aimed to validate WISP1 as a novel adipokine. Human adipocyte differentiation was associated with increased WISP1 expression and secretion. Stimulation of human macrophages with WISP1 led to a proinflammatory response. Circulating WISP1 and WISP1 subcutaneous adipose tissue expression were regulated by weight changes in humans and mice. WISP1 expression in visceral and subcutaneous fat tissue was associated with markers of insulin resistance and inflammation in glucose-tolerant subjects. In patients with nonalcoholic fatty liver disease, we found no correlation among disease activity score, liver fat content, and WISP1 expression. Insulin regulated WISP1 expression in adipocytes in vitro but had no acute effect on WISP1 gene expression in subcutaneous fat tissue in overweight subjects who had undergone hyperinsulinemic clamp experiments. The data suggest that WISP1 may play a role in linking obesity to inflammation and insulin resistance and could be a novel therapeutic target for obesity.

Bioavailability and metabolism of benzyl glucosinolate in humans consuming Indian cress (Tropaeolum majus L.).

SCOPE Benzyl isothiocyanate (BITC), which occurs in Brassicales, has demonstrated chemopreventive potency and cancer treatment properties in cell and animal studies. However, fate of BITC in human body is not comprehensively studied. Therefore, the present human intervention study investigates the metabolism of the glucosinolate (GSL) glucotropaeolin and its corresponding BITC metabolites. Analyzing BITC metabolites in plasma and urine should reveal insights about resorption, metabolism, and excretion. METHODS AND RESULTS Fifteen healthy men were randomly recruited for a cross-over study and consumed 10 g freeze-dried Indian cress as a liquid preparation containing 1000 μmol glucotropaeolin. Blood and urine samples were taken at several time points and investigated by LC-ESI-MS/MS after sample preparation using SPE. Plasma contained high levels of BITC-glutathione (BITC-GSH), BITC-cysteinylglycine (BITC-CysGly), and BITC-N-acetyl-L-cysteine (BITC-NAC) 1-5 h after ingestion, with BITC-CysGly appearing as the main metabolite. Compared to human plasma, the main urinary metabolites were BITC-NAC and BITC-Cys, determined 4-6 h after ingestion. CONCLUSION This study confirms that consumption of Indian cress increases the concentration of BITC metabolites in human plasma and urine. The outcome of this human intervention study supports clinical research dealing with GSL-containing innovative food products or pharmaceutical preparations.

The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism.

Effects of Palatinose and Sucrose Intake on Glucose Metabolism and Incretin Secretion in Subjects With Type 2 Diabetes.

Excessive sugar intake is associated with higher risk of insulin resistance and type 2 diabetes (T2D) (1). Recently, we reported that Palatinose (isomaltulose), a 1,6-linked glucose-fructose dimer that is completely digested and absorbed in the small intestine (2), improved glucose homeostasis and prevented fatty liver compared with 1,2-linked sucrose. Palatinose intake reduced postprandial glucose-dependent insulinotropic peptide (GIP) and insulin release in mice (3). Postprandial insulin secretion and glycemic excursions are regulated by the stimulation of incretin hormones. These intestinal peptides are glucagon-like peptide 1 (GLP-1) and GIP (4). We compared the effects of sucrose versus Palatinose intake on glucose metabolism, insulin and glucagon secretions, and endogenous responses of incretins in T2D participants. In a randomized within-subject crossover study with ≥7 days washout period, 10 overnight-fasted T2D subjects (2 women and 8 men, aged 61 ± 4.6 years, BMI 32.1 ± 4.06 kg/m2) received 50 g of Palatinose (BENEO GmbH, Mannheim, Germany) or sucrose (Sudzucker, Mannheim, Germany) dissolved in 300 mL of tap …

Liver Fat Scores Moderately Reflect Interventional Changes in Liver Fat Content by a Low-Fat Diet but Not by a Low-Carb Diet

Background: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. Aim: We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Methods: Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Results: Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775–0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and changes of measures of obesity, ΔTG, and ΔALT (all low-fat, only) and between ΔIHL and ΔGGT (low-carb, only). With exception for a stronger decrease of triglycerides (TG) levels in the low-carb diet, there is no statistically significant difference in the effect of the diets on anthropometric or serum-based score parameters. Conclusion: While liver fat indices have proved useful in the early detection of NAFLD and may serve as a cost-saving substitute for expensive MR measurements in the cross-sectional evaluation of liver status, their capability to represent interventional changes of liver fat content appears to be diet-specific and lacks accuracy. Liver fat reduction by low-fat diets can be monitored with moderate precision, while low-carb diets require different measuring techniques to demonstrate the same dietary effect.

Dietary Rapeseed Oil Supplementation Reduces Hepatic Steatosis in Obese Men

Obesity is associated with nonalcoholic fatty liver disease (NAFLD) leading to increased hepatic glucose production. NAFLD is one of the most frequent liver diseases however, effective treatment is limited. Animal studies showed a reduction in hepatic steatosis with dietary alpha linoleic acid, which is highly enriched in rapeseed oil (RA). In this study we used a nutritional therapeutic approach and investigated the effect of an isocaloric diet supplemented with RA or olive oil (OL) on liver fat content, endogenous glucose production, total body insulin sensitivity and serum lipids in obese humans suffering from NAFLD. 27 obese men (BMI 30-35, age 18-65) consumed an isocaloric diet including 50 g of either RA (n=12) or OL (n=15) daily for eight weeks. Hepatic MRI, hyperinsulinemic-euglycemic clamp studies with isotope labelled glucose and blood tests were performed prior to and at the end of the study to assess liver fat content, endogenous glucose production and cholesterol and free fatty acid levels, respectively. Body fat content and BMI did not change over the time of intervention for RA and OL. At the end of the study a significant reduction in hepatic fat content (P=0.038) could be observed for RA (13.09±1.61 before vs. 11.14±1.58% after intervention) vs. OL (13.29±2.52 before vs. 15.73±2.74% after intervention). For RA, a 21% reduction (P Disclosure M. Kruse: None. M. Kemper: None. S. Gancheva: None. D. Dannenberger: None. D.F. Markgraf: None. M. Roden: Speaker9s Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. A.F. Pfeiffer: None.

Oral administration of nasturtium affects peptide YY secretion in male subjects

SCOPE Nasturtium plants contain the glucosinolate glucotropaeolin and its corresponding breakdown product benzyl isothiocyanate (BITC), the latter being intensively studied with regard to cancer chemoprevention and anti-inflammatory properties. In addition, recent research has shown that isothiocyanates are able to activate the release of several gut hormones in vitro and in rodent studies. Here, we tested the effects of a dietary nasturtium administration on circulating levels of gut hormones in humans. METHODS AND RESULTS Metabolically healthy males (n = 15) received a single oral dose of 10 g freeze-dried nasturtium leaf material suspended in water or only water (control). Blood samples were taken every hour and serum concentrations of insulin, C-peptide, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and peptide (PYY) were analyzed. Oral nasturtium intake resulted in an increased release of PYY over a time period of 6 h whereas circulating levels of other hormones were not changed. CONCLUSION Given the finding that nasturtium consumption enhances secretion of PYY, a key hormone involved in energy regulation, special diets containing nasturtium, or supplementation with nasturtium or BITC might be considered in the treatment of obesity.