Lebanon is an eastern Mediterranean country inhabited by approximately four million people with a wide variety of ethnicities and religions, including Muslim, Christian, and Druze. In the present study, 926 Lebanese men were typed with Y-chromosomal SNP and STR markers, and unusually, male genetic variation within Lebanon was found to be more strongly structured by religious affiliation than by geography. We therefore tested the hypothesis that migrations within historical times could have contributed to this situation. Y-haplogroup J∗(xJ2) was more frequent in the putative Muslim source region (the Arabian Peninsula) than in Lebanon, and it was also more frequent in Lebanese Muslims than in Lebanese non-Muslims. Conversely, haplogroup R1b was more frequent in the putative Christian source region (western Europe) than in Lebanon and was also more frequent in Lebanese Christians than in Lebanese non-Christians. The most common R1b STR-haplotype in Lebanese Christians was otherwise highly specific for western Europe and was unlikely to have reached its current frequency in Lebanese Christians without admixture. We therefore suggest that the Islamic expansion from the Arabian Peninsula beginning in the seventh century CE introduced lineages typical of this area into those who subsequently became Lebanese Muslims, whereas the Crusader activity in the 11th–13th centuries CE introduced western European lineages into Lebanese Christians.

The Phoenicians were the dominant traders in the Mediterranean Sea two thousand to three thousand years ago and expanded from their homeland in the Levant to establish colonies and trading posts throughout the Mediterranean, but then they disappeared from history. We wished to identify their male genetic traces in modern populations. Therefore, we chose Phoenician-influenced sites on the basis of well-documented historical records and collected new Y-chromosomal data from 1330 men from six such sites, as well as comparative data from the literature. We then developed an analytical strategy to distinguish between lineages specifically associated with the Phoenicians and those spread by geographically similar but historically distinct events, such as the Neolithic, Greek, and Jewish expansions. This involved comparing historically documented Phoenician sites with neighboring non-Phoenician sites for the identification of weak but systematic signatures shared by the Phoenician sites that could not readily be explained by chance or by other expansions. From these comparisons, we found that haplogroup J2, in general, and six Y-STR haplotypes, in particular, exhibited a Phoenician signature that contributed > 6% to the modern Phoenician-influenced populations examined. Our methodology can be applied to any historically documented expansion in which contact and noncontact sites can be identified.

Previous studies have linked aspartame consumption to impaired retention of learned behavior in rodents. Prenatal exposure to aspartame has also been shown to impair odor-associative learning in guinea pigs; and recently, aspartame-fed hyperlipidemic zebrafish exhibited weight gain, hyperglycemia and acute swimming defects. We therefore investigated the effects of chronic lifetime exposure to aspartame, commencing in utero , on changes in blood glucose parameters, spatial learning and memory in C57BL/6J mice. Morris Water Maze (MWM) testing was used to assess learning and memory, and a random-fed insulin tolerance test was performed to assess glucose homeostasis. Pearson correlation analysis was used to investigate the associations between body characteristics and MWM performance outcome variables. At 17 weeks of age, male aspartame-fed mice exhibited weight gain, elevated fasting glucose levels and decreased insulin sensitivity compared to controls (P<0.05). Females were less affected, but had significantly raised fasting glucose levels. During spatial learning trials in the MWM (acquisition training), the escape latencies of male aspartame-fed mice were consistently higher than controls, indicative of learning impairment. Thigmotactic behavior and time spent floating directionless was increased in aspartame mice, who also spent less time searching in the target quadrant of the maze (P<0.05). Spatial learning of female aspartame-fed mice was not significantly different from controls. Reference memory during a probe test was affected in both genders, with the aspartame-fed mice spending significantly less time searching for the former location of the platform. Interestingly, the extent of visceral fat deposition correlated positively with non-spatial search strategies such as floating and thigmotaxis, and negatively with time spent in the target quadrant and swimming across the location of the escape platform. These data suggest that lifetime exposure to aspartame, commencing in utero, may affect spatial cognition and glucose homeostasis in C57BL/6J mice, particularly in males.

BackgroundRecent evidence suggests that the effects of certain food additives may be synergistic or additive. Aspartame (ASP) and Monosodium Glutamate (MSG) are ubiquitous food additives with a common moiety: both contain acidic amino acids which can act as neurotransmitters, interacting with NMDA receptors concentrated in areas of the Central Nervous System regulating energy expenditure and conservation. MSG has been shown to promote a neuroendocrine dysfunction when large quantities are administered to mammals during the neonatal period. ASP is a low-calorie dipeptide sweetener found in a wide variety of diet beverages and foods. However, recent reports suggest that ASP may promote weight gain and hyperglycemia in a zebrafish nutritional model.MethodsWe investigated the effects of ASP, MSG or a combination of both on glucose and insulin homeostasis, weight change and adiposity, in C57BL/6 J mice chronically exposed to these food additives commencing in-utero, compared to an additive-free diet. Pearson correlation analysis was used to investigate the associations between body characteristics and variables in glucose and insulin homeostasis.ResultsASP alone (50 mg/Kgbw/day) caused an increase in fasting blood glucose of 1.6-fold, together with reduced insulin sensitivity during an Insulin Tolerance Test (ITT) P < 0.05. Conversely MSG alone decreased blood triglyceride and total cholesterol (T-CHOL) levels. The combination of MSG (120 mg/Kgbw/day) and ASP elevated body weight, and caused a further increase in fasting blood glucose of 2.3-fold compared to Controls (prediabetic levels); together with evidence of insulin resistance during the ITT (P < 0.05). T-CHOL levels were reduced in both ASP-containing diets in both genders. Further analysis showed a strong correlation between body weight at 6 weeks, and body weight and fasting blood glucose levels at 17 weeks, suggesting that early body weight may be a predictor of glucose homeostasis in later life.ConclusionsAspartame exposure may promote hyperglycemia and insulin intolerance. MSG may interact with aspartame to further impair glucose homeostasis. This is the first study to ascertain the hyperglycemic effects of chronic exposure to a combination of these commonly consumed food additives; however these observations are limited to a C57BL/6 J mouse model. Caution should be applied in extrapolating these findings to other species.

It has previously been shown that patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in both hepatic and adipose tissue metabolism, and the dietary factors that contribute to the pathogenesis of NAFLD are likely to be multifactorial. Using C57BL/6J mice, we examined whether chronic exposure to low‐dose dietary monosodium glutamate (MSG), high‐fructose corn syrup (HFCS), or a combination of the two, vs. control would affect metabolism and hepatic and visceral fat gene expression in adult male progeny. A maternal diet containing 20% HFCS and/or dietary MSG (97.2 ± 6.3 mg/kg body weight (bw), provided in the drinking water) was offered ad libitum from 3 weeks before mating, and continued throughout gestation and weaning until the progeny reached 32 weeks of age. Liver and abdominal fat gene expression was compared with control animals fed isocaloric standard chow under identical conditions. HFCS induced hepatic steatosis and increased the expression of genes involved in carbohydrate and lipid metabolism. Conversely, dietary MSG elevated serum free fatty acids (FFAs), triglycerides (TGs), high‐density lipoprotein‐cholesterol (HDL‐C), and insulin, together with the expression of hepatic genes involved in lipid metabolism and bile synthesis. The HFCS+MSG combination elevated hepatic TGs, serum FFAs, and TG levels. In visceral white adipose tissue, both MSG and HFCS diets increased the expression of transcription factor Srebf2 and decreased expression of Ppargc1a, while downregulating the expression of mitochondrial respiratory chain components. MSG increased the expression of several genes implicated in adipocytes differentiation. We hypothesize that HFCS may promote hepatic steatosis, whereas dietary MSG induces dyslipidemia and markers of insulin resistance.

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Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. It is also a predisposing factor for type 2 diabetes. Dietary factors are believed to contribute to all three diseases. NAFLD is characterized by increased intrahepatic fat and mitochondrial dysfunction, and its etiology may be attributed to excessive fructose intake. Consumption of high fructose corn syrup‐55 (HFCS‐55) stands at up to 15% of the average total daily energy intake in the United States, and is linked to weight gain and obesity. The aim of this study was to establish whether HFCS‐55 could contribute to the pathogenesis of NAFLD, by examining the effects of HFCS‐55 on hepatocyte lipogenesis, insulin signaling, and cellular function, in vitro and in vivo. Exposure of hepatocytes to HFCS‐55 caused a significant increase in hepatocellular triglyceride (TG) and lipogenic proteins. Basal production of reactive oxygen metabolite (ROM) was increased, together with a decreased capacity to respond to an oxidative challenge. HFCS‐55 induced a downregulation of the insulin signaling pathway, as indicated by attenuated ser473phosphorylation of AKT1. The c‐Jun amino‐terminal kinase (JNK), which is intimately linked to insulin resistance, was also activated; and this was accompanied by an increase in endoplasmic reticulum (ER) stress and intracellular free calcium perturbation. Hepatocytes exposed to HFCS‐55 exhibited mitochondrial dysfunction and released cytochrome C (CytC) into the cytosol. Hepatic steatosis and mitochondrial disruption was induced in vivo by a diet enriched with 20% HFCS 55; accompanied by hypoadiponectinemia and elevated fasting serum insulin and retinol‐binding protein‐4 (RBP4) levels. Taken together our findings indicate a potential mechanism by which HFCS‐55 may contribute to the pathogenesis of NAFLD.

Most cases of juvenile-onset diabetes (JOD) are diagnosed as type 1 diabetes (T1D), for which genetic studies conducted in outbred Caucasian populations support the concept of multifactorial inheritance. However, this view may be partly challenged in particular population settings. In view of the suggestive evidence for a high prevalence of Wolfram syndrome (WFS) in Lebanon, the phenotypic variability associated with WFS1 mutations, and the high consanguinity rate in Lebanon, we aimed to evaluate the contribution of WFS1 mutations as monogenic determinants to JOD in Lebanon. We performed a family-based genetic study, with linkage analysis followed by systematic mutation screening of WFS1 exons in all JOD probands. The study population consisted of an unbiased recruitment of all juvenile-onset insulin-dependent diabetic patients from a specialized diabetes pediatric clinic in Beirut, Lebanon. Homozygous or compound heterozygous WFS1 mutations were found in 22 of the 399 JOD probands (5.5%), resulting in WFS (17 probands) or in non-syndromic non-autoimmune diabetes mellitus (DM, five probands). These accounted for 12.1% (21/174) of probands in consanguineous families, compared with 0.4% (1/225) in non-consanguineous families. Of the 38 patients identified with homozygous or compound heterozygous WFS1 mutations, 11 (29%) had non-syndromic DM, all of whom carried a particular WFS1 mutation, WFS1(LIB), encoding a protein with an extended C-terminal domain. This mutation resulted in a delayed onset or absence of extrapancreatic features. These results underscore the major impact of population-specific factors, such as population-specific mutations and founder effects, and family structure in the genetic determinism of JOD.