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Selected Publication:
Sagmeister, M.
Murine Hepatic Microcirculatory Changes during Sepsis and Obesity - The Role of Leptin
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2015. pp.
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- Authors Med Uni Graz:
- Sagmeister Manfred Gerald
- Advisor:
- Singer Georg
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- Abstract:
- Background: Both, clinical obesity, as a predisposition for several diseases, and sepsis, as a leading cause of death in critically ill patients, are global major health care problems at all ages. There is lack of knowledge regarding the microcirculatory changes of the liver in sepsis under the influence of obesity. Methods: We used intravital microscopy (IVM) to quantify leukocyte as well as platelet rolling and adhesion in hepatic postcapillary venules in either sham operated or septic mice. Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in lean wild type (WT) mice, two genetically altered models of obesity, namely, db/db and ob/ob mice, as well as a diet induced obesity (DIO) group. To determine the role of the adipocytokine leptin, which is, inter alia, responsible for the sense of satiety, we exogenously supplied leptin subcutaneously in a leptin deficient mouse group (ob/ob + leptin). Results: Increased leukocyte rolling was seen in sham operated leptin deficient obese mice (ob/ob and ob/ob + leptin), whereas leukocyte adhesion was highest in the high caloric fed group (DIO), with nearly no changes in platelet recruitment in the non-septic sham groups. CLP induced sepsis increased the number of rolling leukocytes in DIO and ob/ob groups associated with a reversibility by leptin treatment. Leukocyte adherence was highest in septic WT mice, followed by DIO and ob/ob + leptin group, whereby the most heavy db/db mice had lowest sticking leukocyte counts. Platelet rolling was significantly increased in septic ob/ob mice, whereas a reduction of about 50% was demonstrated when treated with leptin. The ob/ob group had significantly elevated platelet adhesion and leptin treatment had no protective effect. Conclusions: The findings of this study indicate that the environment of diet induced obesity compared to genetically altered models of obesity reacts differently in an inflammatory state such as sepsis, as demonstrated in our murine hepatic microcirculation model. Leptin plays likely a key role in the mediation of inflammatory responses and is probably receptor– and blood-level depended.