Hepatic serine and lipid metabolism drive diabetic peripheral neuropathy

Type 2 diabetes represents a disease spectrum in which chronic metabolic dysfunction damages multiple organ systems including liver, kidneys, and peripheral nerves1,2. While onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidemia3-7, aberrant amino acid metabolism also contributes to pathogenesis of diabetes and potentially its complications8-10. Serine and glycine are closely related non-essential amino acids11,12 that are consistently reduced in patients with metabolic syndrome10,13-16, but the mechanistic drivers of serine deficiency and the downstream metabolic and phenotypic consequences remain unclear. Low systemic serine, a serine-opathy, is also emerging as a hallmark of macular and peripheral nerve disorders. Specifically, serine deficiency correlates positively with impaired visual acuity and peripheral neuropathy (PN)17-19. Here we demonstrate that aberrant serine homeostasis in the liver drives serine and glycine deficiencies in genetically obese and hyperglycaemic mice. This serine-opathy can be diagnosed with a serine tolerance test that quantifies systemic serine disposal. Mimicking these metabolic alterations via dietary serine/glycine restriction together with high fat intake dramatically accelerates thermal hypoalgesia in mice and reduces epidermal sensory nerve density, which are accompanied by extensive sciatic nerve lipid remodeling. These phenotypes were subsequently normalized by myriocin, linking serine-associated PN with sphingolipid biosynthesis. These findings identify systemic serine deficiency and dyslipidemia as novel risk factors for PN that may be exploited therapeutically.

Dietary Fat Intake and KRAS Mutations in Colorectal Cancer in a Moroccan Population

Epidemiologic data support an association between diet and mutations in the Kirsten-ras (KRAS) gene involved in colorectal cancer (CRC) development. This study aimed to explore the associations between fat intake and KRAS mutations in codons 12 and 13 in cases of CRC in the Moroccan population. A multicenter case-series study nested in a large-scale Moroccan CRC case-control study was conducted. Among all CRC cases recruited, 151 specimens were available for the DNA mutation analysis. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cis) for KRAS mutation status according to the fat intake variables. A KRAS mutation was detected in the CRC tumor of 34.4% of the patients among whom 65.4% had a single mutation at codon 12 and 34.6% had a single mutation at codon 13. Compared to low levels of consumption, a positive association was observed between high polyunsaturated fatty acids (PUFA) consumption (>16.9 g/day) and prevalence of KRAS mutations (OR = 2.15, 95% CI = 1.01–4.59). No statistically significant associations were observed for total fat, monounsaturated fatty acids, saturated fatty acids and KRAS mutations. The results of this study suggest that PUFA may be relevant in the etiology of CRC, possibly through the generation of G > A transitions at the KRAS oncogene. Further studies are needed to verify and explain this finding.

Effect of the interaction between physical activity and estimated macronutrient intake on HbA1c: population-based cross-sectional and longitudinal studies

IntroductionHealthy diet and physical activity (PA) are essential for preventing type 2 diabetes, particularly, a combination of diet and PA. However, reports on interaction between PA and diet, especially from large epidemiological studies, are limited. We investigated the effect of interaction between PA and macronutrient intake on hemoglobin A1c (HbA1c) levels in the general population.Research design and methodsWe conducted a cross-sectional study of 55 469 men and women without diabetes who participated in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. A self-administered questionnaire ascertained PA and macronutrient intake (carbohydrate, fat, and protein). Multiple linear regression analyses were performed to adjust for confounding variables and examine the interactions. In addition, we conducted a longitudinal study during a 5-year period within a subcohort (n=6881) with accelerometer-assessed PA data.ResultsOverall, PA had a weak inverse association (β=−0.00033, p=0.049) and carbohydrate intake had a strong positive association (β=0.00393, p<0.001) with HbA1c. We observed a tendency of interactions between PA and carbohydrate or fat intake, but not protein intake, on HbA1c levels after adjusting for age, sex, study area, total energy intake, alcohol consumption, smoking, and medication for hypertension or hypercholesterolemia (Pinteraction=0.054, 0.006, and 0.156, respectively). The inverse associations between PA and HbA1c level were more evident in participants with high-carbohydrate (or low-fat) intake than in participants with low-carbohydrate (or high-fat) intake. Although further adjustment for body mass index slightly attenuated the above interactions (Pinteraction=0.098 for carbohydrate and 0.068 for fat), the associations between PA and HbA1c level in stratified analyses remained unchanged. Similar associations and interactions were reproduced in the longitudinal study.ConclusionsThe present results suggest that the effect of PA on HbA1c levels is modified by intake of macronutrient composition.

Health and Nutritional Status of Certain Lactating Mothers of Bahawalpur, Pakistan

Diet is the vital part to survive, and balanced diet is the key to better and healthy living. Our daily needs of the body depend upon food to intake for better and proper functioning of vital organs and all organs. These include carbohydrates, proteins, fats, vitamins, and minerals. The amount required for living is much lowers then required for the nourishing an offspring. Lactation is an astonishing procedure in which the mother's body makes a secretion that has no immediate advantage to them but may completely support the baby. It was descriptive hospital-based study conducted among lactating mothers visiting Bahawal Victoria Hospital, Bahawalpur Pakistan. Sample size comprised of 200 lactating mothers. The Chi-square statistical test was used to analyze the difference between the groups by SPSS of latest version. The results revealed that groups of Body mass index (BMI), age groups, breast feeding status, working status, health status, family income, family member, mode of delivery, infant age status, parity, energy intake, protein intake, fat intake and carbohydrate intake had statistically significant differences while the educational status had no significant differences. In this study dietary intake pattern of lactating mother was normal because mostly mothers were educated, they have good knowledge of balanced diet

Dairy Product Consumption and Oligo-Astheno-Teratozoospermia Risk: A Hospital-Based Case-Control Study in China

Background: Researches on the association of dairy products consumption with Oligo-astheno-teratozoospermia (OAT) risk has been limited and controversial. Therefore, we aim to explore the aforementioned association among Chinese men.Methods: A hospital-based case-control study was conducted in men consisting of 106 cases of OAT and 581 controls. Intakes of dairy products and their related nutrients were collected using a semi-quantitative food frequency questionnaire and semen quality was analyzed according to the World Health Organization guidelines. The daily intake of dairy products and their related nutrients was categorized into three groups with the lowest tertile serving as the reference category. Odds ratios (ORs) and 95% confidence intervals (CIs) of association between dairy intake and OTA risk were calculated by the multivariable logistic regression models.Results: No significant association was found between total dairy (OR T3vs.T1 =1.53, 95% CI: 0.85–2.78), protein (OR T3vs.T1 =1.51, 95% CI: 0.84–2.75), or calcium (OR T3vs.T1 = 1.46, 95% CI: 0.81–2.66) and the OAT risk in the main findings. However, we observed a statistically significant positive association of dairy fat intake with OAT risk (OR T3vs.T1 =1.93, 95% CI: 1.06–3.58). The findings were consistent with the main results when we carried out subgroup analysis stratified by body mass index.Conclusion: A significant positive association was found between dairy fat intake and the risk of OAT. Further large-scale prospective studies are required to confirm this finding.

Overview of Macro Nutrient Intake and Nutritional Status of Students at the Putri Hidayatullah Islamic Boarding School, Ternate City

Adolescents are one of the nutritionally vulnerable groups. At this time, adolescents enter the second phase of rapid growth and then physical growth declines as young adults enter. Problems that arise in adolescents are undernutrition and overnutrition. One that is related to nutritional status is nutrient intake which is very influential on a person's nutritional status. Nutrient intake is influenced by eating habits and eating patterns of adolescents themselves. The purpose of this study was to determine the description of macronutrient intake and nutritional status at the Putri Hidayatullah Islamic Boarding School, Ternate City. The type of research used is descriptive research. The sampling technique used total sampling with a total sample of 29 people. The tools used were Microtoise, Bathroom Scale and form food recall 24. The results showed that the intake of macronutrients, as many as 28 people (96.6%) with less energy intake, 29 people (100.0%) with less protein intake, 16 people (55.2%) with more fat intake and 26 people (89.7%) with less carbohydrate intake. There were 25 people (86.2%) with normal nutritional status. It was concluded that from the results of the respondents had less protein intake and most had less energy and carbohydrate intake. On the other hand, most of these teenagers have good fat intake with normal nutritional status.

Local accumbens in vivo imaging during deep brain stimulation reveals a strategy-dependent amelioration of hedonic feeding

Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used in vivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role in vivo imaging can play in understanding effects of such novel therapies.