Paul Klemm

Max Planck Institute for Metabolism Research | NF · Neuronal Control of Metabolism

Promoting brown adipose tissue (BAT) activity innovatively targets obesity and metabolic disease. While thermogenic activation of BAT is well understood, the rheostatic regulation of BAT to avoid excessive energy dissipation remains ill-defined. Here, we demonstrate that adenylyl cyclase 3 (AC3) is key for BAT function. We identified a cold-inducib...

The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions. However, our understanding of the underlying cellular components and circuitry, have, until recently, emerged primarily from rodent studies. Here, we combine a single-nucleus sequencing database of 433,369 human hypothalamic cells, with spatia...

Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketog...

Dopamine acts on neurons in the arcuate nucleus (ARC) of the hypothalamus, which controls homeostatic feeding responses. Here we demonstrate a differential enrichment of dopamine receptor 1 (Drd1) expression in food intake–promoting agouti related peptide (AgRP)/neuropeptide Y (NPY) neurons and a large proportion of Drd2-expressing anorexigenic pro...

Objective Nonalcoholic fatty liver disease (NAFLD) ranges from steatosis to nonalcoholic steatohepatitis (NASH), which often progresses to hepatocellular carcinoma (HCC) through a largely undefined mechanism. NASH and HCC depend on inflammatory signaling, whose master regulator is the NFκB transcription factor family, activated by canonical and non...

The hypothalamus plays a key role in coordinating fundamental body functions. Despite recent progress in single-cell technologies, a unified catalog and molecular characterization of the heterogeneous cell types and, specifically, neuronal subtypes in this brain region are still lacking. Here, we present an integrated reference atlas, ‘HypoMap,’ of...

Promoting brown adipose tissue (BAT) activity has been recognized as innovative therapeutic approach to improve obesity and metabolic disease. Whilst the molecular circuitry underlying thermogenic activation of BAT is well understood, the processes underlying rheostatic regulation of BAT to maintain homeostasis and avoid excessive energy dissipatio...

Insulin acts on neurons and glial cells to regulate systemic glucose metabolism and feeding. However, the mechanisms of insulin access in discrete brain regions are incompletely defined. Here we show that insulin receptors in tanycytes, but not in brain endothelial cells, are required to regulate insulin access to the hypothalamic arcuate nucleus....

The wake-active orexin system plays a central role in the dynamic regulation of glucose homeostasis. Here we show orexin receptor type 1 and 2 are predominantly expressed in dorsal raphe nucleus-dorsal and -ventral, respectively. Serotonergic neurons in ventral median raphe nucleus and raphe pallidus selectively express orexin receptor type 1. Inac...

Pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the hypothalamus represent key regulators of metabolic homeostasis. Electrophysiological and single-cell sequencing experiments have revealed a remarkable degree of heterogeneity of these neurons. However, the exact molecular basis and functional consequences of this heterogen...

Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance and have previously been shown to up-regulate the expression of the P2Y purinoreceptor 6 (P2Y6R) upon high fat diet (HFD)-induced obesity. Here, we reveal that NK cell-specific inactivation of the P2Y6R gene improves insulin sensitivity in obese mice an...

The maternal perinatal environment modulates brain formation, and altered maternal nutrition has been linked to the development of metabolic and psychiatric disorders in the offspring. Here, we showed that maternal high-fat diet (HFD) feeding during lactation in mice elicits long-lasting changes in gene expression in the offspring's dopaminergic ci...

Melanin-concentrating hormone (MCH)-expressing neurons are key regulators of energy and glucose homeostasis. Here, we demonstrate that they provide dense projections to the median eminence (ME) in close proximity to tanycytes and fenestrated vessels. Chemogenetic activation of MCH neurons as well as optogenetic stimulation of their projections in t...

Supplemental Information PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding

Calorie-rich diets induce hyperphagia and promote obesity, although the underlying mechanisms remain poorly defined. We find that short-term high-fat-diet (HFD) feeding of mice activates prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus of the hypothalamus (ARC). PNOCARC neurons represent a previously unrecognized GABAergic populati...

Obesity and type 2 diabetes mellitus are global emergencies and long noncoding RNAs (lncRNAs) are regulatory transcripts with elusive functions in metabolism. Here we show that a high fraction of lncRNAs, but not protein-coding mRNAs, are repressed during diet-induced obesity (DIO) and refeeding, whilst nutrient deprivation induced lncRNAs in mouse...

Medical visualization research typically aims at clinical medicine, e.g. improved support for diagnosis and treatment planning. Our work, in contrast, aims at the public health sector, where prevention of diseases is the major task. An important branch of public health is epidemiology, an interdisciplinary area that involves medical and statistical...

Background Next-Generation Sequencing (NGS) has been widely accepted as an essential tool in molecular biology. Reduced costs and automated analysis pipelines make the use of NGS data feasible even for small labs, yet the methods for interpreting the data are not sophisticated enough to account for the amount of information. Results We propose s ·...

Epidemiology characterizes the influence of causes to disease and health conditions of defined populations. Cohort studies are population-based studies involving usually large numbers of randomly selected individuals and comprising numerous attributes, ranging from self-reported interview data to results from various medical examinations, e.g., blo...

Epidemiological population studies impose information about a set of subjects to characterize disease-specific risk factors. Population studies comprise heterogeneous variables (features) describing the medical condition as well as demographic and lifestyle factors. The data are analyzed using a priori defined hypotheses to find statistically signi...

Epidemiological studies comprise heterogeneous data about a subject group to define disease-specific risk factors. These data contain information (features) about a subject's lifestyle, medical status as well as medical image data. Statistical regression analysis is used to evaluate these features and to identify feature combinations indicating a d...

Epidemiology aims to provide insight into disease causations. Hence, subject groups (cohorts) are analyzed to correlate the subjects' varying lifestyles, their medical properties and diseases. Recently, these cohort studies comprise medical image data. We assess potential relations between image-derived variables of the lumbar spine with lower back...

A rising number of epidemiological studies apply imaging technologies. Images are not features themselves but provide raw data from which features are extracted. Different to other applications of analysis of medical images the data is analyzed statistically across the cohort. It results in unique requirements regarding the development of methods t...

Epidemiology characterizes the influence of causes to disease and health conditions of defined populations. Cohort studies are population-based studies involving usually large numbers of randomly selected individuals and comprising numerous attributes, ranging from self-reported interview data to results from various medical examinations, e.g., blo...

Epidemiological population studies impose information about a set of subjects (a cohort) to characterize disease-specific risk factors. Cohort studies comprise heterogenous variables describing the medical condition as well as demographic and lifestyle factors and, more recently, medical image data. We propose an Interactive Visual Analysis (IVA) a...

Longitudinal epidemiological studies like the Study of Health in Pomerania (SHIP) analyze a group of thousands of subjects (a cohort) by imposing a multitude of socio-demographic and biological factors. Epidemiological findings rest upon hypotheses which yield a selection of disease-specific cohort study parameters. They are then analyzed for sig-n...

The toponome of a cell describes the location and topological distribution of proteins across the cell. In topo-nomics, the toponome is imaged and its inner structure and its semantics are investigated in order to understand how cells encode different functionalities both in health and disease. Toponome imaging results in complex multi-parameter da...

In epidemiological studies, a group of people with common characteristics or experiences (a cohort) is studied including an analysis of socio-demographic as well as biological factors and correlations indicating per subject the absolute risk of getting a disease. Longitudinal studies are carried out over years or even decades comprising up to thous...