The lipid phosphatase LPP3 regulates extra-embryonic vasculogenesis and axis patterning

Bioactive phospholipids, which include sphingosine-1-phosphate, lysophosphatidic acid, ceramide and their derivatives regulate a wide variety of cellular functions in culture such as proliferation, apoptosis and differentiation. The availability of these lipids and their products is regulated by the lipid phosphate phosphatases (LPPs). Here we show that mouse embryos deficient fo

Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress

Compelling evidence has shown that, besides its putative effect on the regulation of the gonadal axis, estradiol (E2) exerts a dichotomic effect on the hypothalamus to regulate food intake and energy expenditure. The anorectic effect of E2 is mainly mediated by its action on the arcuate nucleus (ARC), whereas its effects on brown adipose tissue (BAT) thermogenesis occur in the ventromedial nucleus (VMH). Here, we demonstrate that central E2 decreases hypothalamic ceramide levels and endoplasmic reticulum (ER) stress. Pharmacological or genetic blockade of ceramide synthesis and amelioration of ER stress selectively occurring in the VMH recapitulate the effect of E2, leading to increased BAT thermogenesis, weight loss, and metabolic improvement. These findings demonstrate that E2 regulation of ceramide-induced hypothalamic lipotoxicity and ER stress is an important determinant of energy balance, suggesting that dysregulation of this mechanism may underlie some changes in energy homeostasis seen in femalesThe research leading to these results has received funding from Xunta de Galicia (R.N.: 2015-CP080 and 2016-PG057; M.L.: 2015-CP079), MINECO co-funded by the FEDER Program of EU (R.N.: BFU2015-70664R; D.P.: SAF2016-77526-R; C.D.: BFU2017-87721; M.L.: SAF2015-71026-R and BFU2015-70454-REDT/Adipoplast). The CiMUS is supported by the Xunta de Galicia (2016-2019, ED431G/05). L.L.-P. is a recipient of a fellowship from Xunta de Galicia (ED481A-2016/094); E.R.-P. is a recipient of a fellowship from MINECO (BES-2015-072743); A.E.-S. is a recipient of a fellowship from MINECO (FPI/BES-2016-077439); C.R. is a recipient of a fellowship from MINECO (FPU16/04582). CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIIIS

Brain Ceramide Metabolism in the Control of Energy Balance

The regulation of energy balance by the central nervous system (CNS) is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D). Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate), the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA) to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance

Brain Ceramide Metabolism in the Control of Energy Balance

International audienceThe regulation of energy balance by the central nervous system (CNS) is a key actor of energy homeostasis in mammals, and deregulations of the fine mechanisms of nutrient sensing in the brain could lead to several metabolic diseases such as obesity and type 2 diabetes (T2D). Indeed, while neuronal activity primarily relies on glucose (lactate, pyruvate), the brain expresses at high level enzymes responsible for the transport, utilization and storage of lipids. It has been demonstrated that discrete neuronal networks in the hypothalamus have the ability to detect variation of circulating long chain fatty acids (FA) to regulate food intake and peripheral glucose metabolism. During a chronic lipid excess situation, this physiological lipid sensing is impaired contributing to type 2 diabetes in predisposed subjects. Recently, different studies suggested that ceramides levels could be involved in the regulation of energy balance in both hypothalamic and extra-hypothalamic areas. Moreover, under lipotoxic conditions, these ceramides could play a role in the dysregulation of glucose homeostasis. In this review we aimed at describing the potential role of ceramides metabolism in the brain in the physiological and pathophysiological control of energy balance

Rôle du biostat sphingolipidique dans l'apoptose des cellules b pancréatiques induite par la gluco-lipotoxicité

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Role of hypothalamic de novo ceramides synthesis in obesity and associated metabolic disorders

International audienceSphingolipid-mediated signalling pathways are described as important players in the normal functioning of neurons and nonneuronal cells in the central nervous system (CNS)

Serum ceramides could predict durable diabetes remission following gastric bypass surgery

Morbid obesity is a major risk factor for the development of type 2 diabetes (T2D). One strategy to both lose weight and counteract T2D is bariatric surgery (RYGB). In a study published in this issue of Med, Poss et al. revealed that circulating ceramides could predict the durability of T2D remission independently of weight loss following RYGB

Régulation du métabolisme lipidique par les hormones thyroïdiennes

Pour la troisième année, dans le cadre du module d’enseignement « Physiopathologie de la signalisation » proposé par l’université Paris-sud, les étudiants du Master « Biologie Santé » de l’université Paris-Saclay se sont confrontés à l’écriture scientifique. Ils ont sélectionné 8 articles scientifiques récents dans le domaine de la signalisation cellulaire présentant des résultats originaux, via des approches expérimentales variées, sur des thèmes allant des relations hôte-pathogène aux innovations thérapeutiques, en passant par la signalisation hépatique et le métabolisme. Après un travail préparatoire réalisé avec l’équipe pédagogique, les étudiants, organisés en binômes, ont ensuite rédigé, guidés par des chercheurs, une Nouvelle soulignant les résultats majeurs et l’originalité de l’article étudié. Ils ont beaucoup apprécié cette initiation à l’écriture d’articles scientifiques et, comme vous pourrez le lire, se sont investis dans ce travail avec enthousiasme ! Deux de ces Nouvelles sont publiées dans ce numéro, les autres l’ont été dans les numéros précédents