Genotypic and Allelic Distribution of the CD36 rs1761667 Polymorphism in High-Level Moroccan Athletes: A Pilot Study.

Previous studies have shown that variations in the CD36 gene may affect phenotypes associated with fat metabolism as the CD36 protein facilitates the transport of fatty acids to the mitochondria for oxidation. However, no previous study has tested whether variations in the CD36 gene are associated with sports performance. We investigated the genotypic and allelic distribution of the single-nucleotide polymorphism (SNP) rs1761667 in the CD36 gene in elite Moroccan athletes (cyclists and hockey players) in comparison with healthy non-athletes of the same ethnic origin. Forty-three Moroccan elite male athletes (nineteen cyclists and twenty-four field hockey players) belonging to the national teams of their respective sports (athlete group) were compared to twenty-eight healthy, active, male university students (control group). Genotyping of the CD36 rs1761667 (G>A) SNP was performed via polymerase chain reaction (PCR) and Sanger sequencing. A chi-square (χ2) test was used to assess the Hardy-Weinberg equilibrium (HWE) and to compare allele and genotype frequencies in the "athlete" and "control" groups. The genotypic distribution of the CD36 rs1761667 polymorphism was similar in elite athletes (AA: 23.81, AG: 59.52, and GG: 16.67%) and controls (AA: 19.23, AG: 69.23, and GG: 11.54%; χ2 = 0.67, p = 0.71). However, the genotypic distribution of the CD36 rs1761667 polymorphism was different between cyclists (AA: 0.00, AG: 72.22, and GG: 27.78%) and hockey players (AA: 41.67, AG: 50.00, and GG: 8.33%; χ2 = 10.69, p = 0.004). Specifically, the frequency of the AA genotype was significantly lower in cyclists than in hockey players (p = 0.02). In terms of allele frequency, a significant difference was found between cyclists versus field hockey players (χ2 = 7.72, p = 0.005). Additionally, there was a predominance of the recessive model in cyclists over field hockey players (OR: 0.00, 95% CI: 0.00-0.35, p = 0.002). Our study shows a significant difference between cyclists and field hockey players in terms of the genotypic and allelic frequency of the SNP rs1761667 of the CD36 gene. This divergence suggests a probable association between genetic variations in the CD36 gene and the type of sport in elite Moroccan athletes.

Reproductive Profile of Neuronal Androgen Receptor Knockout Female Mice With a Low Dose of DHT.

Hyperandrogenism and polycystic ovarian syndrome result from the imbalance or increase of androgen levels in females. Androgen receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron-specific AR knockout (KO) mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone, and estradiol were comparable between the control and the SynARKO mice. There were no differences in cyclicity and fertility between the control and SynARKO mice, with similar impairment in both groups on DHT treatment. Neuronal AR KO, as in this SynARKO mouse model, did not alleviate the infertility associated with DHT treatment. These studies suggest that neuronal AR KO neither altered reproductive function under physiological androgen levels, nor restored fertility under hyperandrogenic conditions.

Association between "cluster of differentiation 36 (CD36)" and adipose tissue lipolysis during exercise training: a systematic review.

Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36 (CD36) gene. This receptor has a high affinity for fatty acids and is involved in lipid metabolism. An abundance of FAT/CD36 during exercise occurs in mitochondria and solitary muscles. As such, we aimed to systematically review the evidence for the relationship FAT/CD36 and adipose tissue lipolysis during exercise training. Five electronic databases were selected for literature searches until June 2022: PubMed, Web of Science, Scopus, science direct, and Google Scholar. We combined the different synonyms and used the operators ("AND", "OR", "NOT"): (CD36 gene) OR (CD36 polymorphism) OR (cluster of differentiation 36) OR (FAT/CD36) OR (fatty acid translocase) OR (platelet glycoprotein IV) OR (platelet glycoprotein IIIb) AND (adipose tissue lipolysis) OR (fatty acids) OR (metabolism lipid) OR (adipocytes) AND (physical effort) OR (endurance exercise) OR (high-intensity training). All published cross-sectional, cohort, case-control, and randomized clinical trials investigating CD36 polymorphisms and adipose tissue lipolysis during exercise in subjects (elite and sub-elite athletes, non-athletes, sedentary individuals and diabetics), and using valid methods to measure FAT/CD36 expression and other biomarkers, were considered for inclusion in this review. We initially identified 476 publications according to the inclusion and exclusion criteria, and included 21 studies investigating FAT/CD36 and adipose tissue lipolysis during exercise in our systematic review after examination of titles, abstracts, full texts, and quality assessments using the PEDro scale. There were nine studies with male-only participants, three with female-only participants, and nine studies included both female and male participants. There were 859 participants in the 21 selected studies. Studies were classified as either low quality (n = 3), medium quality (n = 13), and high quality (n = 5). In general, the data suggests an association between FAT/CD36 and adipose tissue lipolysis during exercise training. Improvements in FAT/CD36 were reported during or after exercise in 6 studies, while there were no changes reported in FAT/CD36 in 4 studies. An association between fat oxidation and FAT/CD36 expression during exercise was reported in 7 studies. No agreement was reached in 5 studies on FAT/CD36 content after dietary changes and physical interventions. One study reported that FAT/CD36 protein expression in muscle was higher in women than in men, another reported that training decreased FAT/CD36 protein in insulin-resistant participants, while another study reported no differences in FAT/CD36 in young, trained individuals with type 2 diabetes. Our analysis shows an association between FAT/CD36 expression and exercise. Furthermore, an association between whole-body peak fat oxidation and FAT/CD36 expression during exercise training was demonstrated. Systematic Review Registration: [PROSPERO], identifier [CRD42022342455].

Prevalence and antimicrobial susceptibility profile of Salmonella isolated from food products in the region of Casablanca, Morocco.

INTRODUCTION: Salmonellosis is a foodborne bacterial disease responsible for food epidemics around the world. The objective of this study is to determine the prevalence and diversity of Salmonella serotypes in several food products isolated at the Casablanca Regional Analysis and Research Laboratory and to test their resistance to different antimicrobials. METHODOLOGY: The isolation and identification of Salmonella were performed according to Moroccan standard 08.0.116. All isolates were serotyped and were then tested for antibiotic resistance using the disk diffusion method. The Salmonella isolates were further analyzed by PCR to detect the presence of virulence genes invA. RESULTS: 20 different serotypes were identified from 80 strains isolated from 2015 to 2019, the most common of which are S. kentucky (26.3%) followed by S. muenster (10%), S. typhimurium (8.7%), S. menston (7.5%) and S. enteritidis (6.3%). Antimicrobial susceptibility testing revealed that 66.25% of isolates were resistant to at least one of the 14 antimicrobial agents tested. Bacterial resistance was most frequently observed for tetracycline with 46.25%, 45% to sulfonamide, 35% to nalidixic acid, 26, 25% to ampicillin, and 25% to ciprofloxacin. Salmonella serotypes S. montevideo, S. virchow, S. amsterdam, S. anatum, and S. bloomsbury were 100% susceptible to all antimicrobials tested. Examination of Salmonella for invA gene was positive for all the strains. CONCLUSIONS: The results of this study have shown that minced meat has a high level of Salmonella contamination, which can be considered one of the main potential sources of human salmonellosis in Morocco.

Metabolic Rewiring in Glioblastoma Cancer: EGFR, IDH and Beyond.

Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans' foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells' metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy.

Brain Insulin Signaling, Alzheimer Disease Pathology, and Cognitive Function.

OBJECTIVE: To examine associations of molecular markers of brain insulin signaling with Alzheimer disease (AD) and cognition among older persons with or without diabetes. METHODS: This clinical-pathologic study was derived from a community-based cohort study, the Religious Orders Study. We studied 150 individuals (mean age at death =87 years, 48% women): 75 with and 75 without diabetes (matched by sex on age at death and education). Using enzyme-linked immunosorbent assay, immunohistochemistry, and ex vivo stimulation of brain tissue with insulin, we assessed insulin signaling in the postmortem middle frontal gyrus cortex. Postmortem data documented AD neuropathology. Clinical evaluations documented cognitive function proximate to death, based on 17 neuropsychological tests. In adjusted regression analyses, we examined associations of brain insulin signaling with diabetes, AD, and level of cognition. RESULTS: Brain insulin receptor substrate-1 (IRS1) phosphorylation (pS307 IRS1/total IRS1) and serine/threonine-protein kinase (AKT) phosphorylation (pT308 AKT1/total AKT1) were similar in persons with or without diabetes. AKT phosphorylation was associated with the global AD pathology score (p = 0.001). In contrast, IRS1 phosphorylation was not associated with AD (p = 0.536). No other associations of insulin signaling were found with the global AD score, including when using the ex vivo brain insulin stimulation method. In secondary analyses, normalized pT308 AKT1 was positively correlated with both the amyloid burden and tau tangle density, and no other associations of brain insulin signaling with neuropathology were observed. Moreover, normalized pT308 AKT1 was associated with a lower level of global cognitive function (estimate = -0.212, standard error = 0.097; p = 0.031). INTERPRETATION: Brain AKT phosphorylation, a critical node in the signaling of insulin and other growth factors, is associated with AD neuropathology and lower cognitive function. ANN NEUROL 2020;88:513-525.

Lipid accumulation and oxidation in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor in adults. Despite the multimodal standard treatments for GBM, the median survival is still about one year. Analysis of brain tissues from GBM patients shows that lipid droplets are highly enriched in tumor tissues while undetectable in normal brain tissues, yet the identity and functions of lipid species in GBM are not well understood. The aims of the present work are to determine how GBM utilizes fatty acids, and assess their roles in GBM proliferation. Treatment of U138 GBM cells with a monounsaturated fatty acid, oleic acid, induces accumulation of perilipin 2-coated lipid droplets containing triglycerides enriched in C18:1 fatty acid, and increases fatty acid oxidation. Interestingly, oleic acid also increases glucose utilization and proliferation of GBM cells. In contrast, pharmacologic inhibition of monoacylglycerol lipase attenuates GBM proliferation. Our findings demonstrate that monounsaturated fatty acids promote GBM proliferation via triglyceride metabolism, suggesting a novel lipid droplet-mediated pathway which may be targeted for GBM treatment.

The gliotransmitter ACBP controls feeding and energy homeostasis via the melanocortin system.

Glial cells have emerged as key players in the central control of energy balance and etiology of obesity. Astrocytes play a central role in neural communication via the release of gliotransmitters. Acyl-CoA binding protein (ACBP)-derived endozepines are secreted peptides that modulate the GABAA receptor. In the hypothalamus, ACBP is enriched in arcuate nucleus (ARC) astrocytes, ependymocytes and tanycytes. Central administration of the endozepine octadecaneuropeptide (ODN) reduces feeding and improves glucose tolerance, yet the contribution of endogenous ACBP in energy homeostasis is unknown. We demonstrated that ACBP deletion in GFAP+ astrocytes, but not in Nkx2.1-lineage neural cells, promoted diet-induced hyperphagia and obesity in both male and female mice, an effect prevented by viral rescue of ACBP in ARC astrocytes. ACBP-astrocytes were observed in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and supressed feeding while increasing carbohydrate utilization via the melanocortin system. Similarly, ACBP overexpression in ARC astrocytes reduced feeding and weight gain. Finally, the ODN-GPCR agonist decreased feeding and promoted weight loss in ob/ob mice. These findings uncover ACBP as an ARC gliopeptide playing a key role in energy balance control and exerting strong anorectic effects via the central melanocortin system.

A novel role for central ACBP/DBI as a regulator of long-chain fatty acid metabolism in astrocytes.

Acyl-CoA-binding protein (ACBP) is a ubiquitously expressed protein that binds intracellular acyl-CoA esters. Several studies have suggested that ACBP acts as an acyl-CoA pool former and regulates long-chain fatty acids (LCFA) metabolism in peripheral tissues. In the brain, ACBP is known as Diazepam-Binding Inhibitor, a secreted peptide acting as an allosteric modulator of the GABAA receptor. However, its role in central LCFA metabolism remains unknown. In the present study, we investigated ACBP cellular expression, ACBP regulation of LCFA intracellular metabolism, FA profile, and FA metabolism-related gene expression using ACBP-deficient and control mice. ACBP was mainly found in astrocytes with high expression levels in the mediobasal hypothalamus. We demonstrate that ACBP deficiency alters the central LCFA-CoA profile and impairs unsaturated (oleate, linolenate) but not saturated (palmitate, stearate) LCFA metabolic fluxes in hypothalamic slices and astrocyte cultures. In addition, lack of ACBP differently affects the expression of genes involved in FA metabolism in cortical versus hypothalamic astrocytes. Finally, ACBP deficiency increases FA content and impairs their release in response to palmitate in hypothalamic astrocytes. Collectively, these findings reveal for the first time that central ACBP acts as a regulator of LCFA intracellular metabolism in astrocytes. Acyl-CoA-binding protein (ACBP) or diazepam-binding inhibitor is a secreted peptide acting centrally as a GABAA allosteric modulator. Using brain slices, cortical, and hypothalamic astrocyte cultures from ACBP KO mice, we demonstrate that ACBP mainly localizes in astrocytes and regulates unsaturated but not saturated long-chain fatty acids (LCFA) metabolism. In addition, ACBP deficiency alters FA metabolism-related genes and results in intracellular FA accumulation while affecting their release. Our results support a novel role for ACBP in brain lipid metabolism. FA, fatty acids; KO, knockout; PL, phospholipids; TAG, triacylglycerol.

α/ß-Hydrolase domain-6-accessible monoacylglycerol controls glucose-stimulated insulin secretion.

Glucose metabolism in pancreatic ß cells stimulates insulin granule exocytosis, and this process requires generation of a lipid signal. However, the signals involved in lipid amplification of glucose-stimulated insulin secretion (GSIS) are unknown. Here we show that in ß cells, glucose stimulates production of lipolysis-derived long-chain saturated monoacylglycerols, which further increase upon inhibition of the membrane-bound monoacylglycerol lipase α/ß-Hydrolase Domain-6 (ABHD6). ABHD6 expression in ß cells is inversely proportional to GSIS. Exogenous monoacylglycerols stimulate ß cell insulin secretion and restore GSIS suppressed by the pan-lipase inhibitor orlistat. Whole-body and ß-cell-specific ABHD6-KO mice exhibit enhanced GSIS, and their islets show elevated monoacylglycerol production and insulin secretion in response to glucose. Inhibition of ABHD6 in diabetic mice restores GSIS and improves glucose tolerance. Monoacylglycerol binds and activates the vesicle priming protein Munc13-1, thereby inducing insulin exocytosis. We propose saturated monoacylglycerol as a signal for GSIS and ABHD6 as a negative modulator of insulin secretion.

Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.

Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.