Angela Kuhla

Angela Kuhla
University of Rostock · Faculty of Medicine

About

52
Publications
3,254
Reads
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794
Citations
Citations since 2017
25 Research Items
548 Citations
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120
2017201820192020202120222023020406080100120

Publications

Publications (52)
Article
Full-text available
Objective Obesity, often associated with non-alcoholic fatty liver disease (NAFLD), is characterized by an imbalance between energy expenditure and food intake, which is also reflected by desensitization of fibroblast growth factor 21 (FGF21). FGF21 is strongly influenced, among others, by TNFα, which is known to be upregulated in obesity-induced i...
Article
Full-text available
Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The non-inbred mouse (Mus musculus) line Titan, also known as DU6, is one of the world’s longest selection experiments for high body mass and was previously described as a model for metabolic healthy (benig...
Poster
Full-text available
Background: Amyloid β (Aβ) plaques are recognized as a main pathological hallmark of Alzheimer´s disease (AD). One important cause for Aβ-plaque formation may be a persistent dysbalance between Aβ production and clearance. In the last years, the so called glymphatic system was identified as main contributor to Aβ clearance from the brain through g...
Article
Full-text available
The endocannabinoid system (ECS) plays a pivotal role in the complex control and regulation of food intake. Pharmacological ECS activation could improve health in energy-deficient stages by increasing food intake, at least in intermittent feeders. However, knowledge of the mechanism regulating appetite in species with continued nutrient delivery is...
Article
Full-text available
Obesity is one of the most challenging diseases of the 21st century and is accompanied by behavioural disorders. Exercise, dietary adjustments, or time-restricted feeding are the only successful long-term treatments to date. Fibroblast growth factor 21 (FGF21) plays a key role in dietary regulation, but FGF21 resistance is prevalent in obesity. The...
Article
Transgenic mouse models serve a better understanding of Alzheimer’s disease (AD) pathogenesis and its consequences on neuronal function. Well-known and broadly used AD models are APPswe/PS1dE9 mice, which are able to reproduce features of amyloid-β (Aβ) plaque formations as well as neuronal dysfunction as reflected in electrophysiological recording...
Article
Full-text available
Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amy...
Article
Background: To date, there are no effective treatments for Alzheimer's disease (AD). Thus, a significant need for research of therapies remains. Objective: One promising pharmacological target is the hormone fibroblast growth factor 21 (FGF21), which is thought to be neuroprotective. A clinical candidate for medical use could be the FGF21 analog...
Article
Full-text available
The literature describes a close correlation between metabolic disorders and abnormal immune responses, like low-grade inflammation (LGI), which may be one mechanistic link between obesity and various comorbidities, including non-alcoholic fatty liver disease (NAFLD). In our study, we investigated the influence of dietary composition on obesity-der...
Article
Full-text available
Background: Strong line of evidence suggests that the increased risk to develop AD may at least be partly mediated by cholesterol metabolism. A key regulator of cholesterol transport is the Apolipoprotein E4 (ApoE4), which plays a fundamental role in neuronal maintenance and repair. Impaired function of ApoE4 may contribute to altered cerebral met...
Article
Full-text available
Acetaminophen (APAP)-induced acute liver failure (ALF) is a life-threatening disease with only a few treatment options available. Though extensive research has been conducted for more than 40 years, the underlying pathomechanisms are not completely understood. Here, we studied as to whether APAP-induced ALF can be prevented in mice by silencing the...
Article
In many animal experiments scientists and local authorities define a body-weight reduction of 20% or more as severe suffering and thereby as a potential parameter for humane endpoint decisions. In this study, we evaluated distinct animal experiments in multiple research facilities, and assessed whether 20% body-weight reduction is a valid humane en...
Article
Full-text available
Rare diseases are a heterogeneous group of very different clinical syndromes. Their most common causes are defects in the hereditary material, and they can therefore be passed on to descendants. Rare diseases become manifest in almost all organs and often have a systemic expressivity, i.e., they affect several organs simultaneously. An effective ca...
Article
The endocannabinoids N-arachidonylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) participate in the control of feed intake and energy metabolism. Most mammals increase their feed intake after parturition to cope with the increased energy and nutrient requirements for milk synthesis, thereby increasing their metabolic rate. Here we investigate...
Article
Epidemiological studies suggest that individuals with diabetes mellitus are at greater risk of developing Alzheimer's disease. A well-known insulin-sensitizing drug and the most widely prescribed oral medication for diabetes is metformin. There is evidence that metformin acts in a neuroprotective manner via the AMPK/mTOR pathway by inhibiting the t...
Article
Full-text available
Niemann-Pick-disease type C1 (NPC1) is an autosomal-recessive cholesterol-storage disorder. Besides other symptoms, NPC1 patients develop liver dysfunction and hepatosplenomegaly. The mechanisms of hepatomegaly and alterations of lipid metabolism-related genes in NPC1 disease are still poorly understood. Here, we used an NPC1 mouse model to study a...
Article
Full-text available
Subjects/methods: sNSE was determined in 901 subjects (499 women, 22-81 years, BMI 18-48 kg/m2), participating in a population-based study (SHIP-TREND). We report age-specific patterns of sNSE levels between males and females. Females showed augmenting, males decreasing sNSE levels associated with age (males: p = 0.1052, females: p = 0.0363). sNSE...
Article
Full-text available
Transgenic animal models of Aβ pathology provide mechanistic insight into some aspects of Alzheimer disease (AD) pathology related to Aβ accumulation. Quantitative neuroimaging is a possible aid to improve translation of mechanistic findings in transgenic models to human end phenotypes of brain morphology or function. Therefore, we combined MRI-bas...
Article
Caloric restriction (CR) decelerates the aging process, extends lifespan and exerts neuroprotective effects in diverse species by so far unknown mechanisms. Based on known neuroprotective effects of fibroblastic growth factor 21 (Fgf21) we speculate that CR upregulates Fgf21, which phosphorylates neuronal AMP-activated protein kinase (AMPK), leadin...
Article
The majority of research has suggested that α-lipoic acid (ALA) is a potential therapeutic agent for chronic diseases associated with oxidative stress, including atherosclerosis, diabetes, and neurodegeneration. Therefore, a nutritional supplementation with ALA is recommended although the effects of a short- and long-term intake of ALA on central o...
Article
Caloric restriction (CR) is a well-described dietary intervention that delays the onset of aging-associated biochemical and physiological changes thereby extending the lifespan of rodents. The influence of CR on metabolism, strength and morphology of bone has been controversially discussed in literature. Thus, the present study evaluated whether li...
Article
Acute liver failure (ALF) is a life threatening disease for which only few treatment options exist. The molecular pathways of disease progression are not well defined, but the death receptor Fas (CD95/Apo-1) appears to play a pivotal role in hepatocyte cell death and the development of ALF. Here, we explored posttranscriptional gene silencing of Fa...
Chapter
The liver with its complex functions in biosynthesis, metabolism, clearance, and host defense plays a central role in the physiology of the human body. Hepatic homeostasis is highly dependent on adequate perfusion and microcirculation. Hereby, the liver presents with unique features, such as the dual hepatic arterial and portal venous blood supply...
Article
Neurons that reenter the cell cycle die rather than divide, a phenomenon that is associated with neurodegeneration in Alzheimer's disease (AD). Reexpression of cell-cycle related genes in differentiated neurons in AD might be rooted in aberrant mitogenic signaling. Because microglia and astroglia proliferate in the vicinity of amyloid plaques, it i...
Article
A variety of data suggesting apoptotic cell death as a key feature of liver injury stimulated researchers to investigate the therapeutic potential of anti-apoptotic strategies in experimental models. However, the overestimated role of apoptotic cell death in liver injury has tempered the clinical translation of the protection afforded by anti-apopt...
Article
Calorie lowering slows the aging process and extends life span in diverse species by so far unknown mechanisms. The inverse linear relationship between calorie intake and life span suggests that regulators of energy metabolism are of importance in aging. The present study shows that lifelong caloric restriction in mice induces a metabolic adaptatio...
Article
Since hyperglycemia aggravates acute pancreatitis and also activates the receptor for advanced glycation endproducts (RAGE) in other organs, we explored if RAGE is expressed in the pancreas and if its expression is regulated during acute pancreatitis and hyperglycemia. Acute pancreatitis was induced by cerulein in untreated and streptozotocin treat...
Article
Background Activation of the receptor for advanced glycation endproducts (RAGE) causes sustained activation of multiple inflammatory pathways. Therefore, RAGE has potential as a new therapeutic target in sepsis. The aim of this study was to analyse whether RAGE blockade in vivo prevents microcirculatory dysfunction and subsequent tissue injury in e...
Article
Full-text available
Caloric restriction (CR) is argued to positively affect general health, longevity and the normally occurring age-related reduction of cognition. This issue is well examined, but most studies investigated the effect of short-term periods of CR. Herein, 4 weeks old female mice were fed caloric restricted for 4, 20 and especially for 74 weeks. CR mice...
Article
Full-text available
Abstract This study evaluates the effect of the H2S donor GYY4137 (GYY) on adhesion molecule expression, protein S-sulfhydration and morphology of platelets in vitro and on kinetics of microvascular thrombus formation in vivo. Using flowcytometry, untreated resting, TRAP-activated, or TRAP-activated and GYY-exposed human platelets were studied for...
Article
Aging often restricts the capacity of the immune system. Endotoxemia is characterized by an immune response initiated by a group of pattern recognition receptors including the receptor for advanced glycation end products (RAGE). The aim of this study was to clarify to which extent RAGE and its signaling pathways such as the so called mitogen-activa...
Article
Full-text available
Aims: Darbepoetin-α (DPO), a long-acting erythropoietin analog, has been shown to protect the liver against cholestatic injury, to exert an antifibrotic effect, and to increase the survival time in a model of common bile duct ligation. Here we evaluate whether these tissue-protective effects are caused by DPO induced regulation of hepatobiliary tr...
Data
Analysis of pancreatitis induced cell expansion, inflammation, pancreas-to-body weight ratio and cell death in one year old mice. Comparison of cerulein (n = 5) with streptozotocin plus cerulein (n = 5) treated mice on day 30 demonstrates that diabetes increases the number of BrdU-positive interstitial cells (a), decreases the number of BrdU-positi...
Data
Detection of infiltrating immune cells. The chloroacetate esterase positive cells (red arrows) depict infiltrated immune cells on day 23 (a-c) and day 30 (d-f) of cerulein (a,d), streptozotocin (b,e) and streptozotocin plus cerulein (c,f) treated mice (Cer: n = 4, STZ: n = 5, STZ + Cer: n = 6). Bar = 5 μm
Article
Full-text available
It is well established that acute pancreatitis often causes diabetes and that a high blood glucose level associated with pancreatitis is a marker of poor prognosis. The aim of this study was to evaluate if diabetes merely reflects the severity of pancreatitis or whether it can also aggravate the progression of this disease in a vicious circle. Reve...
Article
Uncoupling protein-2 (UCP2) might play an important role in mediating ischemia/reperfusion (I/R) injury due to its function in uncoupling of oxidative phosphorylation and in the proton leak-associated increase of reactive oxygen species (ROS) production. The aim of this study was to elucidate the role of UCP2 in hepatic I/R injury. UCP2 wild type a...
Article
The incidence of nonalcoholic fatty liver disease is steadily increasing among the elderly population. Lipid metabolism is transcriptionally controlled by the nuclear receptors retinoid acid receptor alpha, liver-X-receptor alpha, and peroxisome proliferator-activated receptor alpha and their target genes ABCA1, sterol regulatory element-binding pr...
Article
The objective of this study is to clarify whether age-related oxidative stress enhances hepatic vulnerability via increased interaction of advanced glycation endproducts (AGE) with their receptor RAGE. To further address the role of uncoupling of mitochondrial respiration, mitochondrial uncoupling protein-2 wild-type (UCP2+/+) and knock out (UCP2-/...
Article
Mitochondrial dysfunction seems to be intrinsically involved in the pathogenesis of multiple organ failure because of enhanced production of reactive oxygen species and induction of oxidative damage. Chronic oxidative stress in turn causes an accumulation of advanced glycation end products (AGEs). To investigate whether mitochondrial dysfunction-as...
Article
Cytotoxic T lymphocytes and their granule components, such as perforin and granzyme, play an important role in the defense of hepatic infections caused by different pathogens. Moreover, it has been shown in vitro that hepatocytes can initiate cell death via a perforin-dependent mechanism. Although it is well known that hepatocellular apoptosis in D...
Article
Liver injury and cell death are prominent features in the pathogenesis of acute liver failure. Mitochondrial uncoupling protein 2 plays a controversial role in liver cell death through its involvement in the production of reactive oxygen species and adenosine triphosphate. This randomized controlled animal study was designed to investigate the exac...
Article
There is increasing evidence that the active contribution of hepatocytes to liver disease is strongly dependent on local cytokine environment. It has been shown in vitro that TNFalpha can enhance hepatocyte FasLigand (FasL)-mediated cytotoxicity. Here, we demonstrate that TNFalpha-induced apoptosis was associated with Fas and FasL upregulation and...
Chapter
There is increasing evidence that active contribution of the hepatocyte to liver disease is strongly dependent on the local cytokine environment. Most recently, it has been shown in vitro that tumor necrosis factor alpha (TNFα) can enhance hepatocyte FasL-mediated cytotoxicity. The present in vivo study examined the relevance of the Fas/FasL pathwa...
Chapter
Liver cell injury and cell death are prominent features in the pathogenesis of acute liver failure. Mitochondrial Uncoupling Protein 2 (UCP2) plays a controversial role in liver cell death through its involvement in the production of reactive oxygen species and adenosine triphosphate. The present study was designed to investigate the exact role of...

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