obesity genes

SUGAR – Identification of disease-causing molecular targets in obesity-related traits and diabetes by integrating multi-omics layers (Prof. Dr. Markus Scholz)

Our ultimate goal is to identify causal molecular processes that link obesity-related traits with type 2 diabetes as major sequela of obesity. Furthermore, we aim to provide targets to modify these processes. For this purpose, we perform an integrative multi-omics approach in three independent cohorts (Sorbs, LIFE-Adult, LIFE-Heart) for which comparable genetic, transcriptomic, and metabolomic data are available.

Genetic determinants of hyperoxaluria and CaOx-nephrolithiasis in pa-tients after malabsorptive bariatric surgery (PD Dr. Jan Halbritter)

Prevalence of calcium oxalate nephrolithiasis (CaOx-NL) is markedly increased in obese patients after malab-sorptive bariatric surgery. Mechanistically, fat malabsorption is thought to lead to increased enteric oxalate absorption with secondary enteric hyperoxaluria (SEH) and potential CaOx-stone formation. Additionally, loss of enteric colonization with oxalate-digesting bacteria, e.g. Oxalobacter formigenes, may aggravate SEH. Conversely, in primary hyperoxaluria (PH) due to biallelic mutations of either AGXT, GRHPR, or HOGA1, en-dogenous hepatic oxalate overproduction is the underlying mechanism of stone formation. Therefore, the ques-tion arises whether genetic susceptibility predisposes certain patients to develop kidney stones after bariatric surgery.

Bacterial translocation to adipose tissue and metabolic diseases (Prof. Dr. Peter Kovacs)

There is a growing number of studies indicating that the gut flora, its composition, and its functions are altered in obese persons and thus contributes to inflammation processes and metabolic diseases. Trials with animal models with high fat feeding suggest that some obesity associated diseases are due to bacterial influences. Therefor this study examines how bacteria in the adipose tissue, the degree of permeability of the guts, the inflammation of adipose tissue and the stage of obesity are interconnected.

Influence of post-bariatric exercise intervention on epigenetic profile (Prof. Dr. Yvonne Böttcher)

The study examines the influence of a six-month exercise program (endurance and strength training) after bari-atric surgery (Roux-Y-Gastric Bypass) on epigenetic processes in the skeletal muscles, blood and adipose tissue using samples that are taken before and after the exercise program. Epigenetic processes are chemical proce-dures (methylation) on the genomes (DNA) that can be modulated by environmental influences and which affect the gene function. Scientists assume that certain epigenetic influences correlate with adiposity and its ac-companying diseases.

Longitudinal alterations in DNA methylation and association with obesity risk in children (Prof. Dr. Yvonne Böttcher)

Besides the genetic hereditary impact on the obesity risk of a person, epigenetic influences are assumed to play a role. Epigenetic influences on the human genotype are natural chemical processes influencing the DNA (methylation). This DNA-methylation can be modulated by environmental influences, yet methylation does not change the components of the genes (DNA), but it influences the gene function. Methylation can turn specific genes on or off. An early genetic and epigenetic prediction of the obesity risky could be useful for appropriate prevention measures in childhood. This study examines the epigenetic influence on specific areas of the DNA and their potential association with the adiposity risk in later childhood.

Identification and characterization of novel genes with neuronal and astrocytic influence on body weight regulation (Prof. Dr. Peter Kovacs)

In the development of obesity the brain, especially the hypothalamus, plays an important role - besides the adipose tissue. In this brain region energy consumption and eating is being coordinated. Recent studies have detected new obesity risk genes in the brain which influence the emergence of obesity. The complex interaction of certain brain and neuronal cells (neurons and astrocytes) imply the influence of diverse genes in the devel-opment and degree of obesity. The study therefore investigates via DNA-analyses the different impacts of obesity risk genes on neurons and astrocytes in normal- and overweight mice.

Identification of novel obesity genes using congenic rat strains (PD Dr. rer. med. Nora Klöting, completed)

Researchers here try to find genetic factors, which are partly responsible for an increase of the body fat mass and weight. Special rats are being used in this study. It will then be investigated whether the identified genes occur in humans, and which relevance they have.

DNA methylation and adiposity (Prof. Dr. Yvonne Böttcher, completed)

The study examines how far epigenetic mechanisms are involved in the development of adiposity. DNA methylation plays a crucial role. Therefore, methylation analysis of CpG islands in adiposity genes are carried out in the blood and in the adipose tissue. It is tested whether these islands are associated with adiposity.

Metabolic effects of vaspin in a transgenic mouse model (Prof. Dr. Peter Kovacs, completed)

The research team of Prof. Kovacs scrutinizes in a transgenic mouse model the effects of vaspin, which is produced in adipose tissue. It is assumed that vaspin increases the cells response to insulin and thus improves sugar metabolism. If the insulin sensitivity of the cells is reduced a type-2-diabetes is the consequence, as is the case in many obese patients.) Vaspin can be detected in various brain regions (hypothalamus, cerebrospinal fluid). The effect of vaspin on adipose tissue, organs, insulin, brain and eating behaviour will be tested in depth not only in different mouse models but also in transgenic mice.

Cell-specific transcriptome in the hypothalamus of diet-induced obese mice (Prof. Dr. Peter Kovacs, completed)

The potential role of certain genes in different brain cells (astrocytes, neurons mainly in hypothalamus) in the development of obesity is being examined in this research project. Especially the interplay of obesity-risk-genes and neuronal brain cells as well as food-intake and energy metabolism.

The metabolic role of the adhesion G protein-coupled receptor (aGPCR) GPR133 in mouse and human (PD Dr. Dr. Ines Liebscher), abgeschlossen

The cells of the human body have different receptors that regulate the metabolism and the function of the cells. The so-called adhesion G protein-coupled receptors (aGPCR) are associated with severe diseases and metabolic disorders. This study examines one representative of the aGPCR-group (GPR 133) in the animal model and on molecular level. The aim is to clarify the importance of this receptor and its effects on cells, bodyweight and metabolism.