High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis.

Exogenous factors that may influence the pathophysiology of Giardia infection remain incompletely understood. We have investigated the role of dietary fat in the pathogenesis of Giardia infection. Male 3 to 4-week-old C57BL/6 mice were fed either a low fat (LF) or a high fat (HF) diet for 12 days and challenged with G. duodenalis. In infected animals, the trophozoite burden was higher in HF + Giardia mice compared to the LF + Giardia group at day 7 post infection. Fatty acids exerted direct pro-growth effects on Giardia trophozoites. Analysis of disease parameters showed that HF + Giardia mice exhibited more mucosal infiltration by inflammatory cells, decreased villus/crypt ratios, goblet cell hyperplasia, mucus disruption, increased gut motility, and elevated fecal water content compared with LF + Giardia. HF diet-dependent exacerbation of Giardia-induced goblet cell hyperplasia was associated with elevated Atoh1 and Muc2 gene expression. Gut microbiota analysis revealed that the HF diet alone induces a taxonomic shift. HF + Giardia mice exhibited microbiota dysbiosis characterized by an increase of Firmicutes and a decrease of Bacteroidetes and significant changes in α- and ß-diversity metrics. Taken together, the findings suggest that a HF diet exacerbates the outcome of Giardia infection. The data demonstrate that elevated dietary fat represents an important exogenous factor promoting the pathophysiology of giardiasis.

Relationship between carbohydrate-to-fat intake ratio and the development of chronic kidney disease: A community-based prospective cohort study.

BACKGROUND & AIMS: It is well-known that high protein intake is associated with renal hyperfiltration and faster renal function decline, but the association of other macronutrients, carbohydrate and fat, with development of chronic kidney disease (CKD) is still inconclusive. Therefore, we aimed to examine the relationship between fat-to-carbohydrate intake ratio (F/C ratio) and incident CKD. METHODS: We included 9226 subjects from the Korean Genome and Epidemiology Study. The subjects were divided into two groups depending on 1 g protein intake per ideal body weight per day. Primary exposure was the F/C ratio defined as calorie intake of fat/calorie intake of fat and carbohydrate. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 and/or proteinuria (≥1+). RESULTS: During a median follow-up duration of 11.4 years, 778 (8.4%) CKD events occurred. Subjects in the lowest F/C ratio tertile had faster eGFR decline rate than other tertiles. In multivariable Cox analysis, a significantly higher CKD risk was observed in the lowest tertile when protein intake > 1 g/kg/day (hazard ratio [HR] for T1 (<16.1%) vs. T3 (>21.5%), 1.38; 95% confidence interval [CI], 1.03-1.84; P = 0.031). In sensitivity analysis, subjects maintained low F/C ratio diet (<16.1%) during 4 years showed higher risk of subsequent CKD development than those maintained high F/C ratio diet (≥16.1%; HR, 1.70; 95% CI, 1.10-2.63; P = 0.018). In cubic spline analysis, CKD risk was sharply increased in F/C ratio <16.1%, but the risk was nearly constant in F/C ratio ≥16.1%. CONCLUSIONS: A diet with a low F/C ratio was associated with increased risk of CKD in the general population. Therefore, it is necessary to limit excessive high carbohydrate and low fat intake to prevent CKD development in this population.

Investigating the effect of positional variation on mid-lactation mammary gland transcriptomics in mice fed either a low-fat or high-fat diet.

Little attention has been given to the effect of positional variation of gene expression in the mammary gland. However, more research is shedding light regarding the physiological differences that mammary gland location can have on the murine mammary gland. Here we examined the differentially expressed genes between mammary gland positions under either a low-fat diet (LFD) or a high-fat diet (HFD) in the mid-lactation mammary gland (lactation day 11; L11). Three-week old WT C57BL/6 mice were randomly assigned to either a low-fat diet (LFD) or high fat diet (HFD) (n = 3/group) and either the right thoracic mammary gland (TMG) or inguinal mammary gland (IMG) was collected from each dam for a total of 12 unique glands. Within each diet, differentially expressed genes (DEGs) were first filtered by adjusted p-value (cutoff ≤ 0.05) and fold-change (FC, cutoff ≥2). Genes were further filtered by mean normalized read count with a cutoff≥10. We observed that mammary gland position had a significant impact on mammary gland gene expression with either LFD or HFD diet, with 1264 DEGs in LFD dams and 777 DEGs in HFD dams. We found that genes related to snRNP binding and translation initiation were most significantly altered between the TMG and IMG. Although we were not able to discern a molecular mechanism, many small nuclear RNAs and small nucleolar RNAs were differentially expressed between the TMG and IMG responsible for cellular functions such as splicing and ribosome biogenesis, which provides and interesting avenue for future research. Our study supports the hypothesis that collection of the mammary gland from a particular location influences mammary gland gene expression, thereby highlighting the importance for researchers to be vigilant in documenting and reporting which mammary gland they are using for their studies.

Effects of Palm Stearin versus Butter in the Context of Low-Carbohydrate/High-Fat and High-Carbohydrate/Low-Fat Diets on Circulating Lipids in a Controlled Feeding Study in Healthy Humans.

BACKGROUND: Foods rich in saturated fatty acids (SFAs) have been discouraged by virtue of their cholesterol-raising potential, but this effect is modulated by the food source and background level of carbohydrate. OBJECTIVE: We aimed to compare the consumption of palm stearin (PS) versus butter on circulating cholesterol responses in the setting of both a low-carbohydrate/high-fat (LC/HF) and high-carbohydrate/low-fat (HC/LF) diet in healthy subjects. We also explored effects on plasma lipoprotein particle distribution and fatty acid composition. METHODS: We performed a randomized, controlled-feeding, cross-over study that compared a PS- versus a Butter-based diet in a group of normocholesterolemic, non-obese adults. A controlled canola oil-based 'Run-In' diet preceded the experimental PS and Butter diets. All diets were eucaloric, provided for 3-weeks, and had the same macronutrient distribution but varied in primary fat source (40% of the total fat). The same Run-In and cross-over experiments were done in two separate groups who self-selected to either a LC/HF (n = 12) or a HC/LF (n = 12) diet track. The primary outcomes were low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL)-C, triglycerides, and LDL particle distribution. RESULTS: Compared to PS, Butter resulted in higher LDL-C in both the LC/HF (13.4%, p = 0.003) and HC/LF (10.8%, p = 0.002) groups, which was primarily attributed to large LDL I and LDL IIa particles. There were no differences between PS and Butter in HDL-C, triglycerides, or small LDL particles. Oxidized LDL was lower after PS than Butter in LC/HF (p = 0.011), but not the HC/LF group. CONCLUSIONS: These results demonstrate that Butter raises LDL-C relative to PS in healthy normocholesterolemic adults regardless of background variations in carbohydrate and fat, an effect primarily attributed to larger cholesterol-rich LDL particles.

Fat-restricted low-glycemic index diet controls weight and improves blood lipid profile: A pilot study among overweight and obese adults in Southwest China.

ABSTRACT: Evidence from trials demonstrating the benefits and risks of low-glycemic index and fat-restricted diets in weight loss and blood lipid profile changes is unclear. This study aimed to assess the implemented and effects of a fat-restricted low-glycemic index diet on weight control and blood lipid profile changes in in overweight/obese Southwest Chinese individualst.This prospective pilot study enrolled overweight/obese subjects at the People's Hospital of Sichuan Province between February and July 2019. The daily energy intake was reduced by 300 to 500 kcal according to the participant's weight and activity level, with low-glycemic index carbohydrate- and fat-energy ratios < 45% and 25% to 30%, respectively. Participants received guidance for 3 months by telephone follow-up, internet interaction, or WeChat. Changes in weight, body composition, and blood profile were measured.A total of 254 patients were finally analyzed, including 101 males and 153 females. After adjusting for potential confounders, weight (P < .001), body mass index (P < .001), waist circumference (P < .001), waist-hip ratio (P < .001), body fat percentage (P < .001), visceral fat area (P < .001), basal metabolism (P = .002), cholesterol (P < .001), and triglycerides (P < .001) were significantly reduced after the 3-month intervention. The above indexes showed no significant differences between men and women.Regardless of gender, fat-restricted low-glycemic index diet might be helpful for controlling weight and lowering blood cholesterol and triglycerides in overweight/obese individuals in Southwest China.

Low-fat diets and testosterone in men: Systematic review and meta-analysis of intervention studies.

BACKGROUND: Higher endogenous testosterone levels are associated with reduced chronic disease risk and mortality. Since the mid-20th century, there have been significant changes in dietary patterns, and men's testosterone levels have declined in western countries. Cross-sectional studies show inconsistent associations between fat intake and testosterone in men. METHODS: Studies eligible for inclusion were intervention studies, with minimal confounding variables, comparing the effect of low-fat vs high-fat diets on men's sex hormones. 9 databases were searched from their inception to October 2020, yielding 6 eligible studies, with a total of 206 participants. Random effects meta-analyses were performed using Cochrane's Review Manager software. Cochrane's risk of bias tool was used for quality assessment. RESULTS: There were significant decreases in sex hormones on low-fat vs high-fat diets. Standardised mean differences with 95 % confidence intervals (CI) for outcomes were: total testosterone [-0.38 (95 % CI -0.75 to -0.01) P = 0.04]; free testosterone [-0.37 (95 % CI -0.63 to -0.11) P = 0.005]; urinary testosterone [-0.38 (CI 95 % -0.66 to -0.09) P = 0.009]; and dihydrotestosterone [-0.3 (CI 95 % -0.56 to -0.03) P = 0.03]. There were no significant differences for luteinising hormone or sex hormone binding globulin. Subgroup analysis for total testosterone, European and North American men, showed a stronger effect [-0.52 (95 % CI -0.75 to -0.3) P < 0.001]. CONCLUSIONS: Low-fat diets appear to decrease testosterone levels in men, but further randomised controlled trials are needed to confirm this effect. Men with European ancestry may experience a greater decrease in testosterone, in response to a low-fat diet.

Hidden Hunger of Vitamin E among Healthy College Students: A Cross- Sectional Study.

BACKGROUND: College students may have a risk of fat-soluble vitamin deficiencies due to unhealthy dietary habits, especially for vitamin A and E. They are important members of the human antioxidant network; deficiencies of these vitamins may increase the risk of many critical diseases. OBJECTIVE: The current study was undertaken to determine the status of vitamin A and E in college students. METHODS: Healthy college students were recruited, and fasting blood samples of them were collected and used for determining serum levels of retinol and α-tocopherol by the HPLC method. RESULTS: We found that there was no vitamin A deficiency in college students. However, vitamin E deficiency existed in 34.5% of college students, especially in males. All the students had no vitamin E adequacy. In addition, our findings showed that BMI was inversely associated with serum α-- tocopherol, but not serum retinol. CONCLUSION: These results suggest that vitamin E deficiency in college students should be given more attention, and it is necessary to consider using vitamin E supplements.

Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake.

The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m-2 were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal-1) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal-1) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d-1 less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d-1 less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .

Macronutrient composition of the diet and long-term changes in weight and waist circumference in the EPIC-Italy cohort.

BACKGROUND AND AIMS: The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC-Italy - the Italian section of the European Prospective Investigation into Cancer and Nutrition - study. METHODS AND RESULTS: A total of 32,119 participants provided anthropometric measures at recruitment and 12 years later (mean). Diet at recruitment was assessed using validated semi-quantitative food frequency questionnaires. Weight and waist changes associated with replacing 10% of energy from one macronutrient with 10% of energy from another macronutrient were assessed by multivariable linear regression. Increased energy from total protein at the expense of any other macronutrient was significantly associated with increased weight and waist circumference. Increased starch at the expense of sugar and total protein was associated with significantly decreased weight and waist circumference; when starch replaced total fat, weight significantly decreased. Increased sugar at the expense of starch and total fat was significantly associated with increased weight and waist circumference; but increase at the expense of total protein was significantly associated with decreased weight and waist circumference. CONCLUSION: Our results suggest that increasing protein at the expense of fat or carbohydrates, and reducing starch by increasing other macronutrients, might be associated with increased weight and waist gain.

Diet-Induced Obesity Disrupts Trace Element Homeostasis and Gene Expression in the Olfactory Bulb.

The aim of this study was to determine the impact of diet-induced obesity (DIO) on trace element homeostasis and gene expression in the olfactory bulb and to identify potential interaction effects between diet, sex, and strain. Our study is based on evidence that obesity and olfactory bulb impairments are linked to neurodegenerative processes. Briefly, C57BL/6J (B6J) and DBA/2J (D2J) male and female mice were fed either a low-fat diet or a high-fat diet for 16 weeks. Brain tissue was then evaluated for iron, manganese, copper, and zinc concentrations and mRNA gene expression. There was a statistically significant diet-by-sex interaction for iron and a three-way interaction between diet, sex, and strain for zinc in the olfactory bulb. Obese male B6J mice had a striking 75% increase in iron and a 50% increase in manganese compared with the control. There was an increase in zinc due to DIO in B6J males and D2J females, but a decrease in zinc in B6J females and D2J males. Obese male D2J mice had significantly upregulated mRNA gene expression for divalent metal transporter 1, alpha-synuclein, amyloid precursor protein, dopamine receptor D2, and tyrosine hydroxylase. B6J females with DIO had significantly upregulated brain-derived neurotrophic factor expression. Our results demonstrate that DIO has the potential to disrupt trace element homeostasis and mRNA gene expression in the olfactory bulb, with effects that depend on sex and genetics. We found that DIO led to alterations in iron and manganese predominantly in male B6J mice, and gene expression dysregulation mainly in male D2J mice. These results have important implications for health outcomes related to obesity with possible connections to neurodegenerative disease.

Dietary 23-hydroxy ursolic acid protects against diet-induced weight gain and hyperglycemia by protecting monocytes and macrophages against nutrient stress-triggered reprogramming and dysfunction and preventing adipose tissue inflammation.

The aim of this study was to determine whether the atheroprotective phytochemical 23-hydroxy ursolic acid protects against diet-induced obesity and hyperglycemia by preventing nutrient stress-induced monocyte reprogramming. After a two week run-in period on a defined, phytochemical-free low-fat maintenance diet, 12-week old female C57BL/6J mice were either kept on the maintenance diet for additional 13 weeks or switched to either a high-calorie diet, a high-calorie diet supplemented with either 0.05% 23-hydroxy ursolic acid or a high-calorie diet supplemented with 0.2% 23-hydroxy ursolic acid. Dietary supplementation with 23-hydroxy ursolic acid reduced weight gain and adipose tissue mass, prevented hyperglycemia, hyperleptinemia and adipose tissue inflammation, and preserved glucose tolerance. 23-Hydroxy ursolic acid also preserved blood monocyte mitogen-activated protein kinase phosphatase-1 activity, a biomarker of monocyte health, and reduced macrophage content in the adipose tissue. Targeted gene profiling by qRT-PCR using custom-designed TaqMan® Array Cards revealed that dietary 23-hydroxy ursolic acid converts macrophages into a transcriptionally hyperactive phenotype with enhanced antioxidant defenses and anti-inflammatory potential. In conclusion, our findings show that dietary 23-hydroxy ursolic acid exerts both anti-obesogenic effects through multiple mechanisms. These include improving glucose tolerance, preventing hyperleptinemia, maintaining blood monocyte function, reducing recruitment of monocyte-derived macrophages into adipose tissues during nutrient stress, and converting these macrophages into an anti-inflammatory, potentially inflammation-resolving phenotype, all contributing to reduced adipose tissue inflammation. Our data suggest that 23-hydroxy ursolic acid may serve as an oral therapeutic and dietary supplement suited for patients at risk for obesity, impaired glucose tolerance and cardiovascular disease.

Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy-mediated degradation.

Metabolic changes in sulfatides and other sulfated glycans have been related to various diseases, including Alzheimer's disease (AD). However, the importance of polyunsaturated fatty acids (PUFA) in sulfated lysosomal substrate metabolism and its related disorders is currently unknown. We investigated the effects of deficiency or supplementation of PUFA on the metabolism of sulfatides and sulfated glycosaminoglycans (sGAGs) in sulfatide-rich organs (brain and kidney) of mice. A PUFA-deficient diet for over 5 weeks significantly reduced the sulfatide expression by increasing the sulfatide degradative enzymes arylsulfatase A and galactosylceramidase in brain and kidney. This sulfatide degradation was clearly associated with the activation of autophagy and lysosomal hyperfunction, the former of which was induced by suppression of the Erk/mTOR pathway. A PUFA-deficient diet also activated the degradation of sGAGs in the brain and kidney and that of amyloid precursor proteins in the brain, indicating an involvement in general lysosomal function and the early developmental process of AD. PUFA supplementation prevented all of the above abnormalities. Taken together, a PUFA deficiency might lead to sulfatide and sGAG degradation associated with autophagy activation and general lysosomal hyperfunction and play a role in many types of disease development, suggesting a possible benefit of prophylactic PUFA supplementation.

Propionic acid and not caproic acid, attenuates nonalcoholic steatohepatitis and improves (cerebro) vascular functions in obese Ldlr-/- .Leiden mice.

The obesity epidemic increases the interest to elucidate impact of short-chain fatty acids on metabolism, obesity, and the brain. We investigated the effects of propionic acid (PA) and caproic acid (CA) on metabolic risk factors, liver and adipose tissue pathology, brain function, structure (by MRI), and gene expression, during obesity development in Ldlr-/- .Leiden mice. Ldlr-/- .Leiden mice received 16 weeks either a high-fat diet (HFD) to induce obesity, or chow as reference group. Next, obese HFD-fed mice were treated 12 weeks with (a) HFD + CA (CA), (b) HFD + PA (PA), or (c) a HFD-control group. PA reduced the body weight and systolic blood pressure, lowered fasting insulin levels, and reduced HFD-induced liver macrovesicular steatosis, hypertrophy, inflammation, and collagen content. PA increased the amount of glucose transporter type 1-positive cerebral blood vessels, reverted cerebral vasoreactivity, and HFD-induced effects in microstructural gray and white matter integrity of optic tract, and somatosensory and visual cortex. PA and CA also reverted HFD-induced effects in functional connectivity between visual and auditory cortex. However, PA mice were more anxious in open field, and showed reduced activity of synaptogenesis and glutamate regulators in hippocampus. Therefore, PA treatment should be used with caution even though positive metabolic, (cerebro) vascular, and brain structural and functional effects were observed.

Diet-regulated behavior: FVB/N mice fed a lean diet exhibit increased nocturnal bouts of aggression between littermates.

The hyperactive FVB/N inbred mouse strain is widely used for transgenic research applications, although rarely for behavioral studies. These mice have visual impairments via retinal degeneration, but are considered highly intelligent and rely largely on olfaction. While investigating diet-induced obesity in autotaxin transgenic FVB/N mice, we observed an increase in the necessity for male, but not female, cage separations. Based on the observations, we hypothesized that feeding FVB/N mice a lean diet increases nocturnal bouts of aggression between male littermates. The diets of adult littermates were switched from normal chow to either ad libitum high-fat (45% fat) or lean (10% fat) matched diets for 27 weeks, whereby the mice reached an average of 43 g versus 35 g, respectively. Then, cage separations due to nocturnal bouts of aggression became mandatory, even though littermates peacefully cohabitated for 10-16 weeks previously. Since the data was of an unusual nature, it required uncommon statistical methods to be engendered to evaluate whether and where significance existed. Therefore, utilizing the randomization and population models, we established a methodology and postulated that either testosterone, the autotaxin transgene or diet alteration was the causal factor. Statistical evaluation demonstrated a significant correlation between cage separations and aggressive behavior associated with the lean-diet-fed mice, not autotaxin. Biochemical data did not appear to explain the behavior. In contrast, energy metabolism highlighted differences between the groups of normally hyperactive mice by diet. This characteristic makes FVB/N male mice unsuitable subjects for long-term studies with lean-diet modifications.

Early Hepatic Oxidative Stress and Mitochondrial Changes Following Western Diet in Middle Aged Rats.

To assess the effect of 4 weeks of high fat-high fructose feeding on whole body composition, energy balance, specific markers of oxidative stress and inflammation, and insulin sensitivity in the liver of middle-aged rats, rats (1 year) were fed a diet rich in saturated fatty acids and fructose (HFF rats), mimicking the "Western diet", and compared with rats of the same age that were fed a low fat diet (LF rats). HFF rats exhibited a significant increase in the gain of body weight, energy, and lipids compared to LF rats. HFF rats also showed hepatic insulin resistance, together with an increase in plasma triglycerides, cholesterol, and tumor necrosis factor alpha. Hepatic lipids, triglycerides and cholesterol were higher in HFF rats, while a significant decrease in Stearoyl-CoA desaturase activity was found in this tissue. A marked increase in the protein amount of complex I, concomitant to a decrease in its contribution to mitochondrial respiration, was found in HFF rats. Lipid peroxidation and Nitro-Tyrosine content, taken as markers of oxidative stress, as well as NADPH oxidase activity, were significantly higher in HFF rats, while the antioxidant enzyme catalase decreased in these rats. Myeloperoxidase activity and lipocalin content increased, while peroxisome proliferator activated receptor gamma decreased in HFF rats. The present results provide evidence that middle-aged rats show susceptibility to a short-term "Western diet", exhibiting altered redox homeostasis, insulin resistance, and early mitochondrial alterations in the liver. Therefore, this type of dietary habits should be drastically limited to pursue a "healthy aging".

Low Carbohydrate and Low-Fat Diets: What We Don't Know and Why we Should Know It.

In the 1940s, the diet-heart hypothesis proposed that high dietary saturated fat and cholesterol intake promoted coronary heart disease in "at-risk" individuals. This hypothesis prompted federal recommendations for a low-fat diet for "high risk" patients and as a preventive health measure for everyone except infants. The low carbohydrate diet, first used to treat type 1 diabetes, became a popular obesity therapy with the Atkins diet in the 1970s. Its predicted effectiveness was based largely on the hypothesis that insulin is the causa prima of weight gain and regain via hyperphagia and hypometabolism during and after weight reduction, and therefore reduced carbohydrate intake would promote and sustain weight loss. Based on literature reviews, there are insufficient randomized controlled inpatient studies examining the physiological significance of the mechanisms proposed to support one over the other. Outpatient studies can be confounded by poor diet compliance such that the quality and quantity of the energy intake cannot be ascertained. Many studies also fail to separate macronutrient quantity from quality. Overall, there is no conclusive evidence that the degree of weight loss or the duration of reduced weight maintenance are significantly affected by dietary macronutrient quantity beyond effects attributable to caloric intake. Further work is needed.

High calories but not fat content of lard-based diet contribute to impaired mitochondrial oxidative phosphorylation in C57BL/6J mice heart.

PURPOSE: High calorie intake leads to obesity, a global socio-economic and health problem, reaching epidemic proportion in children and adolescents. Saturated and monounsaturated fatty acids from animal (lard) fat are major components of the western-pattern diet and its regular consumption leads to obesity, a risk factor for cardiovascular disease. However, no clear evidence exists whether consumption of diet rich in saturated (SFAs) and monounsaturated (MUFAs) fatty acids has detrimental effects on cardiac structure and energetics primarily due to excessive calories. We, therefore, sought to determine the impact of high calories versus fat content in diet on cardiac structure and mitochondrial energetics. METHODS: Six-week-old C57BL/6J mice were fed with high calorie, high lard fat-based diet (60% fat, HFD), high-calorie and low lard fat-based diet (10% fat, LFD), and lower-calorie and fat diet (standard chow, 12% fat, SCD) for 10 weeks. RESULTS: The HFD- and LFD-fed mice had higher body weight, ventricular mass and thickness of posterior and septal wall with increased cardiomyocytes diameter compared to the SCD-fed mice. These changes were associated with a reduction in the mitochondrial oxidative phosphorylation (OXPHOS) complexes I and III activity compared to the SCD-fed mice without significant differences between the HFD- and LFD-fed animals. The HFD-fed animals had higher level of malondialdehyde (MDA) than LFD and SCD-fed mice. CONCLUSIONS: We assume that changes in cardiac morphology and selective reduction of the OXPHOS complexes activity observed in the HFD- and LFD-fed mice might be related to excessive calories with additional effect of fat content on oxidative stress.

Significant changes in hepatic transcriptome and circulating miRNAs are associated with diet-induced metabolic syndrome in apoE3L.CETP mice.

Long-term exposure to excess dietary fat leads to obesity and the metabolic syndrome (MetS). The purpose of the present study was to identify global changes in liver gene expression and circulating miRNAs in a humanized mouse model of diet-induced MetS. Male apoE3L.CETP mice received a high-fat diet (HFD) or a low-fat diet (LFD) for different time periods and the progression of MetS pathology was monitored. A separate group of mice was divided into responders (R) or nonresponders (NR) and received HFD for 16 weeks. We found that mice receiving the HFD developed manifestations of MetS and displayed an increasing number of differentially expressed transcripts at 4, 8, and 12 weeks compared with mice receiving the LFD. Significantly changed genes were functionally annotated to metabolic diseases and pathway analysis revealed the downregulation of genes in cholesterol and fatty acid biosynthesis and upregulation of genes related to lipid droplet formation, which was in line with the development of hepatic steatosis. In the serum of the apoE3L.CETP mice we identified three miRNAs that were upregulated specifically in the HFD group. We found that responder mice have a distinct gene signature that differentiates them from nonresponders. Comparison of the two diet intervention studies revealed a limited number of common differentially expressed genes but the expression of these common genes was affected in a similar way in both studies. In conclusion, the characteristic hepatic gene signatures and serum miRNAs identified in the present study provide novel insights to MetS pathology and could be exploited for diagnostic or therapeutic purposes.

Vitamin K deficiency-induced hemorrhagic shock after thoracentesis: a case report.

BACKGROUND: Vitamin K deficiency results in serious coagulation dysfunction, but hemorrhagic shock is rare. Herein, we describe a case of vitamin K deficiency and abnormality in the path of the intercostal artery, the combination of which led to hemorrhagic shock. CASE PRESENTATION: An 83-year-old woman was hospitalized for suspected gallstones. She developed septic shock after 4 days of hospitalization. We considered cholecystitis or cholangitis and performed abdominal ultrasonography, which revealed gallbladder enlargement, biliary sludge, and hyperplasia of the bile duct wall. Antibiotic treatment with sulbactam/ampicillin (SBT/ABPC) was initiated on day four, and percutaneous transhepatic gallbladder drainage (PTGBD) was performed on day five. The treatment was successful, but the patient developed bilateral pleural effusion because of hypoalbuminemia. We performed drainage for bilateral pleural effusion on days 13 and 17. The patient developed hypotension on day 18; blood tests showed anemia and severe coagulation dysfunction but a normal platelet count. We suspected vitamin K deficiency-induced coagulation dysfunction because of previous antibiotic treatment and restricted diet, and it led to hemorrhagic shock. Massive right hemothorax was observed by computed tomography, and urgent interventional radiology was performed. We observed no injury to the intercostal artery truncus but confirmed an abnormality in the course of the intercostal artery; therefore, we inferred that the cause of hemothorax in this case was injury to a small vessel, not truncus because of the abnormality. Because of the likelihood of rebleeding, we performed coil embolization from the seventh to the ninth intercostal artery. Because we confirmed vitamin K deficiency-induced coagulation dysfunction, we referred to the concentration of protein induced by vitamin K absence/antagonist-II (PIVKA-II), and it was found to increase by 23,000. CONCLUSIONS: A combination of vitamin K deficiency and abnormality in the course of the intercostal artery led to hemorrhagic shock. When using certain antibiotics and restricting diet, it is important to measure coagulation function, even if the platelet count is normal. Further, when thoracentesis is performed, abnormalities in the course of the intercostal artery should be identified. Thoracentesis with ultrasound may prevent hemothorax.

Dietary α-lactalbumin alters energy balance, gut microbiota composition and intestinal nutrient transporter expression in high-fat diet-fed mice.

Recently there has been a considerable rise in the frequency of metabolic diseases, such as obesity, due to changes in lifestyle and resultant imbalances between energy intake and expenditure. Whey proteins are considered as potentially important components of a dietary solution to the obesity problem. However, the roles of individual whey proteins in energy balance remain poorly understood. This study investigated the effects of a high-fat diet (HFD) containing α-lactalbumin (LAB), a specific whey protein, or the non-whey protein casein (CAS), on energy balance, nutrient transporters expression and enteric microbial populations. C57BL/6J mice (n 8) were given an HFD containing either 20 % CAS or LAB as protein sources or a low-fat diet containing CAS for 10 weeks. HFD-LAB-fed mice showed a significant increase in cumulative energy intake (P=0·043), without differences in body weight, energy expenditure, locomotor activity, RER or subcutaneous and epididymal white adipose tissue weight. HFD-LAB intake led to a decrease in the expression of glut2 in the ileum (P=0·05) and in the fatty acid transporter cd36 (P<0·001) in both ileum and jejunum. This suggests a reduction in absorption efficiency within the small intestine in the HFD-LAB group. DNA from faecal samples was used for 16S rRNA-based assessment of intestinal microbiota populations; the genera Lactobacillus, Parabacteroides and Bifidobacterium were present in significantly higher proportions in the HFD-LAB group. These data indicate a possible functional relationship between gut microbiota, intestinal nutrient transporters and energy balance, with no impact on weight gain.