leptin and palmidrol

The objective of this study was to investigate the role of palmitoylethanolamide (PEA) in the regulation of energy homeostasis in goldfish (Carassius auratus). We examined the effects of acute or chronic intraperitoneal treatment with PEA (20 μg·g

Topics: Amides; Animals; Body Weight; CLOCK Proteins; Eating; Energy Metabolism; Ethanolamines; Gene Expression Regulation; Goldfish; Homeostasis; Hypothalamus; Injections, Intraperitoneal; Leptin; Lipid Metabolism; Liver; Locomotion; Palmitic Acids; Peroxisome Proliferator-Activated Receptors; Weight Gain

It has been suggested a role of fatty acid ethanolamides in control of feeding behavior. Among these, palmitoylethanolamide (PEA) has not been directly implicated in appetite regulation and weight gain. The aim of this study was to investigate the effect of PEA on food intake and body weight and the interaction between PEA and hypothalamic leptin signaling in ovariectomized rats. Ovariectomy produced hyperphagia and increased weight gain, making it an useful model of mild obesity. Ovariectomized rats were treated with PEA (30 mg/kg sc) for 5 weeks. Then, blood was collected, and hypothalamus and adipose tissue were removed for histological, cellular, and molecular measurements. We showed that PEA caused a reduction of food intake, body weight, and fat mass. The mechanisms underlying PEA effects involved an improvement in hypothalamic leptin signaling, through a raise in signal transducer and activator of transcription 3 phosphorylation. We also reported that PEA reduced AMP-activated protein kinase-α phosphorylation and modulated transcription of anorectic and orexigenic neuropeptides in the hypothalamus. Moreover, PEA increased AMP-activated protein kinase-α phosphorylation and carnitine palmitoyltransferase 1 transcription in adipose tissue, suggesting an increase in ATP-producing catabolic pathway. PEA also polarized adipose tissue macrophages to M2 lean phenotype, associated to a reduction of inflammatory cytokines/adipokines. To demonstrate the direct effect of PEA on leptin sensitivity without interference of adiposity loss, we obtained consistent data in PEA-treated sham-operated animals and in vitro in SH-SY5Y neuroblastoma cell line. Therefore, our data provide a rationale for the therapeutic use of PEA in obese postmenopausal woman.

Topics: Adenosine Triphosphate; Adipokines; Amides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Weight; Cell Line, Tumor; Cytokines; Eating; Endocannabinoids; Ethanol; Ethanolamines; Fatty Acids; Feeding Behavior; Female; Glucose Tolerance Test; Humans; Leptin; Obesity; Ovariectomy; Palmitic Acids; Phosphorylation; Rats; Rats, Wistar; Signal Transduction; Weight Gain

Peripheral and central endocannabinoids and cognate acylethanolamides (AEs) may play important but distinct roles in regulating energy balance.. We hypothesized that in humans central/peripheral endocannabinoids are differently associated with adiposity and energy expenditure and differ by race.. We examined associations of arachindonoylethanolamide, 2-arachidonoylglycerol, palmitoylethanolamide, and oleoylethanolamide (OEA) assayed in plasma and cerebrospinal fluid (CSF) with race, adiposity, and energy expenditure.. In this monitored clinical inpatient study, CSF was obtained by lumbar puncture in 27 individuals (12 Caucasian, 11 American Indian, and four African-American). Twenty-four hour and sleep energy expenditure were measured by indirect calorimetry in a respiratory chamber.. Samples were analyzed from a previous study originally designed to test a blood-brain barrier leptin transport deficit in human obesity.. CSF (but not peripheral) 2-arachidonoylglycerol was significantly increased in American Indians compared with Caucasians (18.48 ± 6.17 vs. 10.62 ± 4.58 pmol/ml, P < 0.01). In the whole group, peripheral AEs were positively but in CSF negatively associated with adiposity. However, in multivariate models adjusted for the other peripheral and CSF AEs, peripheral arachindonoylethanolamide was the only AE significantly associated with adiposity. Interestingly, CSF OEA concentrations were positively associated with adjusted 24 hour and sleep energy expenditure (r = 0.47, P < 0.05; r = 0.42, P < 0.05), but peripheral OEA was not.. These data indicate a central alteration of the endocannabinoid system in American Indians and furthermore show that AEs in both compartments play an important but distinct role in human energy balance regulation.

Topics: Absorptiometry, Photon; Adiposity; Amides; Anti-Obesity Agents; Arachidonic Acids; Blood Glucose; Cannabinoid Receptor Modulators; Endocannabinoids; Energy Metabolism; Ethanolamines; Ethnicity; Glycerides; Humans; Insulin; Leptin; Palmitic Acids; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Receptor, Cannabinoid, CB1; Rimonabant

The endocannabinoid, arachidonoylethanolamide (AEA), and the peroxisome proliferator-activated receptor (PPAR)-alpha ligand, oleylethanolamide (OEA) produce opposite effects on lipogenesis. The regulation of OEA and its anti-inflammatory congener, palmitoylethanolamide (PEA), in adipocytes and pancreatic beta-cells has not been investigated. We report here the results of studies on acylethanolamide regulation in these cells during obesity and hyperglycaemia, and provide an overview of acylethanolamide role in metabolic control. We analysed by liquid chromatography-mass spectrometry OEA and PEA levels in: 1) mouse 3T3F442A adipocytes during insulin-induced differentiation, 2) rat insulinoma RIN m5F beta-cells kept in 'low' or 'high' glucose, 3) adipose tissue and pancreas of mice with high fat diet-induced obesity (DIO), and 4) in visceral fat or blood of obese or type 2 diabetes (T2D) patients. In adipocytes, OEA levels remain unchanged during differentiation, whereas those of PEA decrease significantly, and are under the negative control of both leptin and PPAR-gamma. PEA is significantly downregulated in subcutaneous adipose tissue of DIO mice. In RIN m5F insulinoma beta-cells, OEA and PEA levels are inhibited by 'very high' glucose, this effect being enhanced by insulin, whereas in cells kept for 24 h in 'high' glucose, they are stimulated by both glucose and insulin. Elevated OEA and PEA levels are found in the blood of T2D patients. Reduced PEA levels in hypertrophic adipocytes might play a role in obesity-related pro-inflammatory states. In beta-cells and human blood, OEA and PEA are down- or up-regulated under conditions of transient or chronic hyperglycaemia, respectively.

Topics: 3T3 Cells; Adipocytes; Adult; Aged; Amides; Animals; Arachidonic Acids; Diabetes Mellitus, Type 2; Endocannabinoids; Energy Metabolism; Ethanolamines; Female; Humans; Insulin-Secreting Cells; Leptin; Male; Mice; Mice, Inbred C57BL; Middle Aged; Models, Biological; Obesity; Oleic Acids; Palmitic Acids; Polyunsaturated Alkamides; PPAR gamma; Review Literature as Topic; Structure-Activity Relationship

N-Palmitoylethanolamide (PEA) is an endogenous lipid secreted by human adipocytes that possesses numerous anti-inflammatory properties. Human adipose tissue can be subjected to modulation of its inflammatory state by lipopolysaccharide (LPS). Here we demonstrate that LPS increases the secretion of interleukin-6 (IL-6) by human mature adipocytes via activation of the NFkappaB pathway. This effect is not inhibited by PEA. Inversely, LPS strongly inhibits adipose cell leptin release, with PEA acting as a potentiator of this inhibitory effect. These actions are not linked to a reduction in leptin gene transcription. Thus, PEA does not have an anti-inflammatory role in the secretion of IL-6 via NFkappaB at the adipocyte level, but instead seems to act at the heart of the LPS-stimulated pathway, which, independently of NFkappaB, inhibits the secretion of leptin.

Topics: Adipocytes; Adult; Amides; Cells, Cultured; Endocannabinoids; Ethanolamines; Humans; Inflammation; Interleukin-6; Leptin; Lipopolysaccharides; Middle Aged; NF-kappa B; Palmitic Acids