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Obesity is a major health problem for many developing and industrial countries. Increasing rates reach almost 50 % of the population in some countries and related metabolic diseases including cardiovascular events and T2DM are challenging the health systems. Adiposity, an increase in body fat mass, is a major hallmark of obesity. Adipose tissue is long known not only to store lipids but also to influence whole-body metabolism including food intake, energy expenditure and insulin sensitivity. Adipocytes can store lipids and thereby protect other tissue from lipotoxic damage. However, if the energy intake is higher than the energy expenditure over a sustained time period, adipose tissue will expand. This can lead to an impaired adipose tissue function resulting in higher levels of plasma lipids, which can affect other tissue like skeletal muscle, finally leading to metabolic complications. Several studies showed beneficial metabolic effects of weight reduction in obese subjects immediately after weight loss. However, weight regain is frequently observed along with potential negative effects on cardiovascular risk factors and a high intra-individual response.
We performed a body weight maintenance study investigating the mechanisms of weight maintenance after intended WR. Therefore we used a low caloric diet followed by a 12-month life-style intervention. Comprehensive phenotyping including fat and muscle biopsies was conducted to investigate hormonal as well as metabolic influences on body weight regulation. In this study, we showed that weight reduction has numerous potentially beneficial effects on metabolic parameters. After 3-month WR subjects showed significant weight and fat mass reduction, lower TG levels as well as higher insulin sensitivity. Using RNA-Seq to analyse whole fat and muscle transcriptome a strong impact of weight reduction on adipose tissue gene expression was observed. Gene expression alterations over weight reduction included several cellular metabolic genes involved in lipid and glucose metabolism as well as insulin signalling and regulatory pathways. These changes were also associated with anthropometric parameters assigning body composition. Our data indicated that weight reduction leads to a decreased expression of several lipid catabolic as well as anabolic genes. Long-term body weight maintenance might be influenced by several parameters including hormones, metabolic intermediates as well as the transcriptional landscape of metabolic active tissues. Our data showed that genes involved in biosynthesis of unsaturated fatty acids might influence the BMI 18-month after a weight reduction phase. This was further supported by analysing metabolic parameters including RQ and FFA levels. We could show that subjects maintaining their lost body weight had a higher RQ and lower FFA levels, indicating increased metabolic flexibility in subjects.
Using this transcriptomic approach we hypothesize that low expression levels of lipid synthetic genes in adipose tissue together with a higher mitochondrial activity in skeletal muscle tissue might be beneficial in terms of body weight maintenance.
Methicillin resistant Staphylococcus aureus (MRSA) is one of the most important antibiotic-resistant pathogens in hospitals and the community. Recently, a new generation of MRSA, the so called livestock associated (LA) MRSA, has emerged occupying food producing animals as a new niche. LA-MRSA can be regularly isolated from economically important live-stock species including corresponding meats. The present thesis takes a methodological approach to confirm the hypothesis that LA-MRSA are transmitted along the pork, poultry and beef production chain from animals at farm to meat on consumers` table. Therefore two new concepts were developed, adapted to differing data sets.
A mathematical model of the pig slaughter process was developed which simulates the change in MRSA carcass prevalence during slaughter with special emphasis on identifying critical process steps for MRSA transmission. Based on prevalences as sole input variables the model framework is able to estimate the average value range of both the MRSA elimination and contamination rate of each of the slaughter steps. These rates are then used to set up a Monte Carlo simulation of the slaughter process chain. The model concludes that regardless of the initial extent of MRSA contamination low outcome prevalences ranging between 0.15 and 1.15 % can be achieved among carcasses at the end of slaughter. Thus, the model demonstrates that the standard procedure of pig slaughtering in principle includes process steps with the capacity to limit MRSA cross contamination. Scalding and singeing were identified as critical process steps for a significant reduction of superficial MRSA contamination.
In the course of the German national monitoring program for zoonotic agents MRSA prevalence and typing data are regularly collected covering the key steps of different food production chains. A new statistical approach has been proposed for analyzing this cross sectional set of MRSA data with regard to show potential farm to fork transmission. For this purpose, chi squared statistics was combined with the calculation of the Czekanowski similarity index to compare the distributions of strain specific characteristics between the samples from farm, carcasses after slaughter and meat at retail. The method was implemented on the turkey and veal production chains and the consistently high degrees of similarity which have been revealed between all sample pairs indicate MRSA transmission along the chain.
As the proposed methods are not specific to process chains or pathogens they offer a broad field of application and extend the spectrum of methods for bacterial transmission assessment.
The relationship between nutrition and the development of chronic diseases including metabolic syndrome, diabetes mellitus, cancer and cardiovascular disease has been well studied. On the other hand, changes in the GH-IGF-1 axis in association with nutrition-related diseases have been reported. The interplay between GH, total IGF-1 and different inhibitory and stimulatory kinds of IGF-1 binding proteins (IGFBPs) results in IGF-1 bioactivity, the ability of IGF-1 to induce phosphorylation of its receptor and consequently its signaling. Moreover, IGF-1 bioactivity is sufficient to reflect any change in the GH-IGF-1 system. Accumulating evidence suggests that both of high protein diet, characterized by increased glucagon secretion, and insulin-induced hypoglycemia increase mortality rate and the mechanisms are unclear. However both of glucagon and insulin-induced hypoglycemia are potent stimuli of GH secretion. The aim of the current study was to identify the impact of glucagon and insulin-induced hypoglycemia on IGF-1 bioactivity as possible mechanisms. In a double-blind placebo-controlled study, glucagon was intramuscularly administrated in 13 type 1 diabetic patients (6 males /7 females; [BMI]: 24.8 ± 0.95 kg/m2), 11 obese subjects (OP; 5/ 6; 34.4 ± 1.7 kg/m2), and 13 healthy lean participants (LP; 6/ 7; 21.7 ± 0.6 kg/m2), whereas 12 obese subjects (OP; 6/ 6; 34.4 ± 1.7 kg/m2), and 13 healthy lean participants (LP; 6/ 7; 21.7 ± 0.6 kg/m2) performed insulin tolerance test in another double-blind placebo-controlled study and changes in GH, total IGF-1, IGF binding proteins (IGFBPs) and IGF-1 bioactivity, measured by the cell-based KIRA method, were investigated. In addition, the interaction between the metabolic hormones (glucagon and insulin) and the GH-IGF-1 system on the transcriptional level was studied using mouse primary hepatocytes. In this thesis, glucagon decreased IGF-1 bioactivity in humans independently of endogenous insulin levels, most likely through modulation of IGFBP-1 and-2 levels. The glucagon-induced reduction in IGF-1 bioactivity may represent a novel mechanism underlying the impact of glucagon on GH secretion and may explain the negative effect of high protein diet related to increased cardiovascular risk and mortality rate. In addition, insulin-induced hypoglycemia was correlated with a decrease in IGF-1 bioactivity through up-regulation of IGFBP-2. These results may refer to a possible and poorly explored mechanism explaining the strong association between hypoglycemia and increased cardiovascular mortality among diabetic patients.