Medium-chain fatty acid receptor GPR84 deficiency leads to metabolic homeostasis dysfunction in mice fed high-fat diet.

Overconsumption of food, especially dietary fat, leads to metabolic disorders such as obesity and type 2 diabetes. Long-chain fatty acids, such as palmitoleate are recognized as the risk factors for these disorders owing to their high-energy content and lipotoxicity. In contrast, medium-chain fatty acids (MCFAs) metabolic benefits; however, their underlying molecular mechanisms remain unclear.

Non-target GC-MS analyses of fecal VOCs in NASH-hepatocellular carcinoma model STAM mice.

The increased incidence of obesity in the global population has increased the risk of several chronic inflammation-related diseases, including non-alcoholic steatohepatitis (NASH)-hepatocellular carcinoma (HCC). The progression from NASH to HCC involves a virus-independent liver carcinogenic mechanism; however, we currently lack effective treatment and prevention strategies. Several reports have suggested that fecal volatile organic compounds (VOCs) are strongly associated with NASH-HCC; therefore, we explored the biomarkers involved in its pathogenesis and progression.

Pathological social withdrawal in autism spectrum disorder: A case control study of hikikomori in Japan.

Introduction: Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of ASD are associated with hikikomori.

Methods: Thirty-nine adult male patients with a diagnosis of ASD attending our outpatient clinic for neurodevelopmental disabilities were subjected to a structured interview regarding social withdrawal, various self-administered questionnaires, and blood tests.

Dietary oleic acid contributes to the regulation of food intake through the synthesis of intestinal oleoylethanolamide.

Introduction: Among the fatty acid ethanolamides (FAEs), oleoylethanolamide (OEA), linoleoylethanolamide (LEA), and palmitoylethanolamide (PEA) are reported to be involved in feeding regulation. In particular, OEA is well characterized as a satiety signal. Following food consumption, OEA is synthesized from oleic acid (OA) an -acyl phosphatidylethanolamine-specific phospholipase D-dependent pathway in the gastroenterocytes, and OEA induces satiety by recruiting sensory fibers.

Medium-chain fatty acids suppress lipotoxicity-induced hepatic fibrosis via the immunomodulating receptor GPR84.

Medium-chain triglycerides (MCTs), which consist of medium-chain fatty acids (MCFAs), are unique forms of dietary fat with various health benefits. G protein-coupled 84 (GPR84) acts as a receptor for MCFAs (especially C10:0 and C12:0); however, GPR84 is still considered an orphan receptor, and the nutritional signaling of endogenous and dietary MCFAs via GPR84 remains unclear. Here, we showed that endogenous MCFA-mediated GPR84 signaling protected hepatic functions from diet-induced lipotoxicity.

Intestinal GPR119 activation by microbiota-derived metabolites impacts feeding behavior and energy metabolism.

Objective: The gastrointestinal tract affects physiological activities and behavior by secreting hormones and generating signals through the activation of nutrient sensors. GPR119, a lipid sensor, is indirectly involved in the secretion of incretins, such as glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, by enteroendocrine cells, while it directly stimulates insulin secretion by pancreatic beta cells. Since GPR119 has the potential to modulate metabolic homeostasis in obesity and diabetes, it has attracted interest as a therapeutic target.

Characterization of cellular phenotypes in neurons derived from induced pluripotent stem cells of male patients with Fabry disease.

Fabry disease (FD) is an X-linked inherited lysosomal metabolism disorder in which globotriaosylceramide (Gb3) accumulates in various organs resulting from a deficiency in alpha-galactosidase A. The clinical features of FD include progressive impairments of the renal, cardiac, and peripheral nervous systems. In addition, patients with FD often develop neuropsychiatric symptoms, such as depression and dementia, which are believed to be induced by the cellular injury of cerebrovascular and partially neuronal cells due to Gb3 accumulation.

Autistic children and adolescents with frequent restricted interest and repetitive behavior showed more difficulty in social cognition during mask-wearing during the COVID-19 pandemic: a multisite survey.

Background: The public health measures enacted in order to control the coronavirus disease (COVID-19) pandemic have caused considerable changes to daily life. For autistic children and adolescents, adapting to the "new normal," including mask-wearing, may be difficult because of their restricted interest and repetitive behavior (RRB) characteristics. We aimed to examine the relationships between RRB characteristics and the impact of mask-wearing on their social communications during the pandemic.

Generation and characterization of motor neuron progenitors and motor neurons using metachromatic leukodystrophy-induced pluripotent stem cells.

The pathological consequences leading to primary storage, autophagy impairment, impaired mitochondrial dynamics, and endoplasmic reticulum (ER) stress on neural cell dysfunction and apoptosis in metachromatic leukodystrophy (MLD) have been poorly elucidated. In the present study, we generated 2 cell lines of patient-specific-induced pluripotent stem cells (iPSCs) and modeled the progression of pathological events during the differentiation of iPSCs to motor neuron progenitors (MNPs) and mature motor neurons (MNs). The iPS cells were generated from two late-infantile MLD patient-derived skin fibroblasts using electroporation or the Sendai virus.

Dietary Medium-Chain Triglyceride Decanoate Affects Glucose Homeostasis Through GPR84-Mediated GLP-1 Secretion in Mice.

Background: Dietary triglycerides are an important energy source; however, their excess intake causes metabolic diseases such as obesity and type 2 diabetes. Medium-chain triglycerides (MCTs) as triglyceride forms of medium-chain fatty acids (MCFAs) are applied to meet the energy demands of athletes, the elderly, and people with stunted growth, because MCFAs are efficiently converted into energy for immediate utilization by the organs and do not accumulate as fat. Although the intake of each MCT type (octanoate; C8:0, decanoate; C10:0, and dodecanoate; C12:0) exhibits beneficial metabolic effects, individual functional differences remain unclear.

Unexpected difficult airway due to an undiagnosed congenital lingual thyroglossal duct cyst in a neonate without stridor: A case report.

Lingual thyroglossal duct cysts can be a rare cause of feeding difficulties in infants. Here, we describe a case of an infant with vomiting and feeding difficulty diagnosed with Hirschsprung's disease. However, she developed an unexpected difficult airway during anesthesia induction due to an undiagnosed lingual thyroglossal duct cyst.

Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes.

Objective: To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM).

Research Design And Methods: Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) ( = 20) or distal pancreatectomy (DP) ( = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months.

Feeding regulation by oleoylethanolamide synthesized from dietary oleic acid.

Oleoylethanolamide (OEA), a well-known satiety factor, is produced during feeding in the proximal intestine. Enterocytes sense oleic acid in dietary fat via CD36 and convert it to OEA through NAPE-PLD dependent or independent pathways. The satiety function of OEA is known to involve peroxisome proliferator-activated receptor type-α (PPAR-α).

Synthetic dietary inulin, Fuji FF, delays development of diet-induced obesity by improving gut microbiota profiles and increasing short-chain fatty acid production.

Background: Dietary fiber, including inulin, promotes health via fermentation products, such as short-chain fatty acids (SCFAs), produced from the fiber by gut microbiota. SCFAs exert positive physiological effects on energy metabolism, gut immunity, and the nervous system. Most of the commercial inulin is extracted from plant sources such as chicory roots, but it can also be enzymatically synthesized from sucrose using inulin producing enzymes.

Ketone body receptor GPR43 regulates lipid metabolism under ketogenic conditions.

Ketone bodies, including β-hydroxybutyrate and acetoacetate, are important alternative energy sources during energy shortage. β-Hydroxybutyrate also acts as a signaling molecule via specific G protein-coupled receptors (GPCRs); however, the specific associated GPCRs and physiological functions of acetoacetate remain unknown. Here we identified acetoacetate as an endogenous agonist for short-chain fatty acid (SCFA) receptor GPR43 by ligand screening in a heterologous expression system.

Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease.

Context: Previous studies have shown that the endocannabinoid system plays a major role in energy metabolism through the actions of its main mediators, 2-arachidonoyl--glycerol (2-AG) and anandamide (AEA).

Objective: We examined serum levels of major endocannabinoid mediators and their association with clinical parameters in patients with end-stage renal disease (ESRD).

Design And Setting: Serum concentrations of 2-AG and AEA were measured in patients on maintenance hemodialysis (MHD) and controls, and correlations with various clinical and laboratory indices were examined.

Gut microbiota confers host resistance to obesity by metabolizing dietary polyunsaturated fatty acids.

Gut microbiota mediates the effects of diet, thereby modifying host metabolism and the incidence of metabolic disorders. Increased consumption of omega-6 polyunsaturated fatty acid (PUFA) that is abundant in Western diet contributes to obesity and related diseases. Although gut-microbiota-related metabolic pathways of dietary PUFAs were recently elucidated, the effects on host physiological function remain unclear.

Free Fatty Acid Receptors in Health and Disease.

Fatty acids are metabolized and synthesized as energy substrates during biological responses. Long- and medium-chain fatty acids derived mainly from dietary triglycerides, and short-chain fatty acids (SCFAs) produced by gut microbial fermentation of the otherwise indigestible dietary fiber, constitute the major sources of free fatty acids (FFAs) in the metabolic network. Recently, increasing evidence indicates that FFAs serve not only as energy sources but also as natural ligands for a group of orphan G protein-coupled receptors (GPCRs) termed free fatty acid receptors (FFARs), essentially intertwining metabolism and immunity in multiple ways, such as via inflammation regulation and secretion of peptide hormones.

NAPE-PLD controls OEA synthesis and fat absorption by regulating lipoprotein synthesis in an in vitro model of intestinal epithelial cells.

Oleoylethanolamide (OEA), a fatty acid ethanolamide (FAE), is a lipid mediator that controls food intake and lipid metabolism. Accumulating data imply the importance of intestinal OEA in controlling satiety in addition to gastrointestinal peptide hormones. Although the biochemical pathway of FAE production has been illustrated, the enzymes responsible for the cleavage of OEA from its precursor N-acyl-phosphatidylethanolamine (NAPE) must be identified among reported candidates in the gut.

Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying the gut microbiota-dependent biotransformation of bile acids.

The consumption of soybean protein has well-known favorable metabolic effects (e.g., reduced body weight, body fat, hyperglycemia, insulin resistance, hepatic steatosis, and lipogenesis).

Dietary mung bean protein reduces high-fat diet-induced weight gain by modulating host bile acid metabolism in a gut microbiota-dependent manner.

The 8-globulin-rich mung bean protein (MPI) suppresses hepatic lipogenesis in rodent models and reduces fasting plasma glucose and insulin levels in obese adults. However, its effects on mitigating high fat diet (HFD)-induced obesity and the mechanism underlying these effects remain to be elucidated. Herein, we examined the metabolic phenotype, intestinal bile acid (BA) pool, and gut microbiota of conventionally raised (CONV-R) male C57BL/6 mice and germ-free (GF) mice that were randomized to receive either regular HFD or HFD containing mung bean protein isolate (MPI) instead of the dairy protein present in regular HFD.

Comparison of the Effects of the 1975 Japanese Diet and the Modern Mediterranean Diet on Lipid Metabolism in Mice.

The Japanese diet and the Mediterranean diet are both known to be good for health, but there had been no direct comparison of their health benefits. In this study, we compared the 1975 Japanese diet, which has been found to have high health benefits, with the 2010 Italian diet, which contributes to the longest life expectancy in Mediterranean countries. Diets were created using one-week menus of the two diets based on FAOSTAT Food Balance Sheets.

Dysfunctional oleoylethanolamide signaling in a mouse model of Prader-Willi syndrome.

Prader-Willi syndrome (PWS), the leading genetic cause of obesity, is characterized by a striking hyperphagic behavior that can lead to obesity, type-2 diabetes, cardiovascular disease and death. The molecular mechanism underlying impaired satiety in PWS is unknown. Oleoylethanolamide (OEA) is a lipid mediator involved in the control of feeding, body weight and energy metabolism.

Similar impressions of humanness for human and artificial singing voices in autism spectrum disorders.

People with autism spectrum disorder (ASD) exhibit impairments in the perception of and orientation to social information related to humans, and some people with ASD show higher preference toward human-like robots than other humans. We speculated that this behavioural bias in people with ASD is caused by a weakness in their perception of humanness. To address this issue, we investigated whether people with ASD detect a subtle difference between the same song sung by human and artificial voices even when the lyrics, melody and rhythm are identical.