👤 Leszek Kaczmarek

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence. Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity. G protein-coupled receptors (GPCRs) are among the main modulators of metabolism and energy balance. They, for instance, regulate appetite and satiety in certain hypothalamic neurons, as well as glucose and lipid metabolism and hormone secretion from adipocytes. Mutations in some GPCRs, such as the melanocortin receptor type 4 (MC4R), have been associated with early-onset obesity. Here, we identified the adhesion GPCR latrophilin 1 (ADGRL1/LPHN1) as a member of the regulating network governing food intake and the maintenance of energy balance. Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity, accompanied by dysregulation of glucose homeostasis. Consistently, we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity. Therefore, we propose that LPHN1 dysfunction is a risk factor for obesity development. Show less

The postsynaptic density proteins 95 (PSD95) and 93 (PSD93) belong to a family of scaffolding proteins, the membrane-associated guanylate kinases (MAGUKs), which are highly enriched in synapses and responsible for organizing the numerous protein complexes required for synaptic development and plasticity. Genetic studies have associated MAGUKs with diseases like autism and schizophrenia, but knockout mice show severe, complex defects with difficult-to-interpret behavioral abnormalities due to major motor dysfunction which is atypical for psychiatric phenotypes. Therefore, rather than studying loss-of-function mutants, we comprehensively investigated the behavioral consequences of reduced PSD95 expression, using heterozygous PSD95 knockout mice (PSD95 Show less

Voltage-gated K(+) channels of the Shaw family (also known as the KCNC or Kv3 family) play pivotal roles in mammalian brains, and genetic or pharmacological disruption of their activities in mice results in a spectrum of behavioral defects. We have used the model system of Caenorhabditis elegans to elucidate conserved molecular mechanisms that regulate these channels. We have now found that the C. elegans Shaw channel KHT-1, and its mammalian homologue, murine Kv3.1b, are both modulated by acid phosphatases. Thus, the C. elegans phosphatase ACP-2 is stably associated with KHT-1, while its mammalian homolog, prostatic acid phosphatase (PAP; also known as ACPP-201) stably associates with murine Kv3.1b K(+) channels in vitro and in vivo. In biochemical experiments both phosphatases were able to reverse phosphorylation of their associated channel. The effect of phosphorylation on both channels is to produce a decrease in current amplitude and electrophysiological analyses demonstrated that dephosphorylation reversed the effects of phosphorylation on the magnitude of the macroscopic currents. ACP-2 and KHT-1 were colocalized in the nervous system of C. elegans and, in the mouse nervous system, PAP and Kv3.1b were colocalized in subsets of neurons, including in the brain stem and the ventricular zone. Taken together, this body of evidence suggests that acid phosphatases are general regulatory partners of Shaw-like K(+) channels. Show less

The aim in this survey was analysis of contribution of exposure to tobacco smoke and selected socioeconomic factors in occurrence of low birth weight. The research was done on the group of 1528 pregnant women. Smoking habit was declared by 18.2% of women and passive exposure to tobacco smoke was stated by 31% of respondents. Significant association between active and passive smoking and socioeconomic status of respondents was observed. Cigarette smoking during pregnancy was the main cause of lower birth weight of newborns. The newborns of actively smoking mothers were lighter of about 332 g according to those ones of mothers who did not smoke and were not exposed to passive smoking, and were lighter than newborns of mothers who were not exposed to passive smoking of about 342 g. Show less

Despite of significant progress in the area of perinatal care, there have been numerous perinatal complications still existing. The health status of mother and newborn is affected by many factors, namely: socio-economical; medical prior to pregnancy and medical through the pregnancy; dietary customs, substance use, including tobacco smoking; health service quality; and risk factors that may occur through fertilization. The active and passive exposure to tobacco smoke in utero have been linked to numerous gestation and delivery complications, including low birth weight, preterm delivery and low Apgar score. In this survey, the awareness of health consequences of active and passive smoking in the population of pregnant women and access to the information of this consequence was assessed. Among of women smoking through their pregnancies, the only 19.7% got the information from their doctors about harmful effect of active and passive smoking, and 16.5% of respondents declared self-awareness on health effects of exposure to the tobacco smoke. Show less