High-fat High-carbohydrate Diet Research Articles

Erythropoietin hyporesponsiveness in non-alcoholic fatty liver disease.

Treatment with erythropoietin (EPO) can correct anaemia in chronic kidney disease (CKD) patients; however, up to 10% exhibit resistance or hyporesponsiveness to EPO. Non-alcoholic fatty liver disease (NAFLD), prevalent liver disease in CKD patients, may limit EPO response because of thrombopoietin deficiency, iron homeostasis disorder and inflammation. Therefore, we hypothesized NAFLD is a risk factor for EPO responsiveness. To test our hypothesis, we evaluated the effect of EPO in healthy rats and rats with NAFLD induced by a high-fat, high-carbohydrate (HFHC) diet. After 12 weeks on the HFHC diet, NAFLD rats showed lower erythroid response to EPO treatment than healthy rats. We, then, determined that the primary cause of EPO hyporesponsiveness could be iron deficiency associated with inflammation, which reduces erythroid cell production. Specifically, the concentrations of hepcidin, ferritin, transferrin and white blood cells in NAFLD rats were 12.8-, 16.4-, 2.51- and 1.40-fold higher than those in healthy rats, respectively. However, erythroid cell types in the bone marrow of NAFLD rats were significantly reduced. In conclusion, our data suggest that NAFLD could be a risk factor for EPO responsiveness, which is attributed to functional iron deficiency associated with inflammation.

Ablation of histone methyltransferase Suv39h2 in hepatocytes attenuates NASH in mice

AimsNon-alcoholic steatohepatitis (NASH) is characterized by aberrant lipid metabolism in hepatocytes. We investigated the involvement of a histone H3K9 methyltransferase Suv39h2 in the pathogenesis of NASH. Methods and materialsNASH is induced by feeding the mice with a high-fat high-carbohydrate (HFHC) diet or a high-fat choline-deficient amino acid defined (HFD-CDAA) diet. The Suv39h2f/f mice were crossbred with the Alb-Cre mice to specifically delete Suv39h2 in hepatocytes. Key findingsAblation of Suv39h2 in hepatocytes improved insulin sensitivity of the mice fed either the HFHC diet or the CDAA-HFD diet. Importantly, Suv39h2 deletion significantly ameliorated NAFLD as evidenced by reduced lipid accumulation, inflammation, and fibrosis in the liver. RNA-seq uncovered Vanin-1 (Vnn1) as a novel transcriptional target for Suv39h2. Mechanistically, Suv39h2 repressed Vnn1 transcription in hepatocytes exposed to free fatty acids. Consistently, Vanin-1 knockdown normalized lipid accumulation in Suv39h2-null hepatocytes. Importantly, a significant correlation between Suv39h2, Vanin-1, and hepatic triglyceride levels was identified in NASH patients. SignificanceOur study uncovers a novel mechanism whereby Suv39h2 may contribute to NASH pathogenesis and suggests that targeting the Suv39h2-Vanin-1 axis may yield novel therapeutic solutions against NASH.

Obesity differentially effects the somatosensory cortex and striatum of TgF344-AD rats

Lifestyle choices leading to obesity, hypertension and diabetes in mid-life contribute directly to the risk of late-life Alzheimer’s disease (AD). However, in late-life or in late-stage AD conditions, obesity reduces the risk of AD and disease progression. To examine the mechanisms underlying this paradox, TgF344-AD rats were fed a varied high-carbohydrate, high-fat (HCHF) diet to induce obesity from nine months of age representing early stages of AD to twelve months of age in which rats exhibit the full spectrum of AD symptomology. We hypothesized regions primarily composed of gray matter, such as the somatosensory cortex (SSC), would be differentially affected compared to regions primarily composed of white matter, such as the striatum. We found increased myelin and oligodendrocytes in the somatosensory cortex of rats fed the HCHF diet with an absence of neuronal loss. We observed decreased inflammation in the somatosensory cortex despite increased AD pathology. Compared to the somatosensory cortex, the striatum had fewer changes. Overall, our results suggest that the interaction between diet and AD progression affects myelination in a brain region specific manner such that regions with a lower density of white matter are preferentially affected. Our results offer a possible mechanistic explanation for the obesity paradox.

Vitis vinifera L. seed standardized extract; a promising therapeutic against metabolic syndrome induced by high-fat/high-carbohydrate diet and streptozotocin in rats

Metabolic syndrome (MetS) is a group of abnormal disorders; hypertension, glucose intolerance, dyslipidemia, proinflammatory, and prothrombotic states, affecting approximately 14 % of the world's population. The potential of grape seeds extract (GSE) supplementation to improve the metabolic disturbances and their related conditions like obesity, type 2 diabetes, and nonalcoholic fatty liver disease was investigated in this study. In-vitro metabolic syndrome assays were investigated through α-amylase, α-glucosidase, lipase, lipoxygenase (LOX), cyclooxygenases (COX-1 and COX-2), renin and angiotensin converting enzyme (ACE) inhibition assays. Additionally, in-vivo rat model of high-fat-high-carbohydrate diet (HFD)-induced MetS was established, where metformin (MT) (200 mg/kg) was used as a reference drug and GSE was given at 100 and 200 mg/kg by oral gavage. GSE was standardized using HPLC analysis for the major reported compound; catechin which should be ≥ 160.76 ± 5.52 μg/mL. Total phenolic content of GSE was 21.12±0.61 µg gallic acid equivalent/1 mg extract and total flavonoid content was 23.81±0.64 µg rutin equivalent/1 mg extract. In-vitro assays revealed the potential of GSE to manage the metabolic syndrome, besides its strong antioxidant capacity. Treatment with GSE (100 mg/kg and 200 mg/kg) markedly (P < 0.05) controlled the weight gain, improved the metabolic pathways (total glucose, cholesterol, triglycerides, AST, and ALT), oxidative stress parameters (MDA, GSH, and catalase) and inflammatory biomarkers in HFD fed rats. GSE downregulated the expression of insulin resistance gene (IR) and some inflammatory related genes (TNF-α and NF-κB), additionally it improved the pathological features of metabolic conditions and upgraded the expression of Nrf2 compared to HFD group. The superior effects were owned to the high dose of GSE, 200 mg/kg b.wt. (P < 0.05, P < 0.001). All results sustenance the beneficial effects of the standardized GSE in the management of metabolic syndrome.

Effectiveness of high-fat and high-carbohydrate diets on body composition and maximal strength after 15 weeks of resistance training

PurposeThe aim of this study was to compare High Carbohydrates Low Fat (HCLF) and Low Carbohydrate High Fat (LCHF) diets in terms of changes in body composition and maximal strength. Patients/methodsThe study involved 48 men aged 25 ​± ​2.5, divided into two groups, one of which (n ​= ​23) was following the LCHF diet and the other (n ​= ​25) the HCLF diet. Both groups performed the same resistance training protocol for 15 weeks. Maximal strength in squat, bench press and deadlift was assessed pre- and post-intervention. Measurements of selected body circumferences and tissue parameters were made using the multifunctional, multi-frequency, direct bioelectric impedance InBody 770 analyzer from InBody Co., Ltd (Cerritos, California, USA). The team with the necessary qualifications and experience in research performed all the measurements and maintained participants’ oversight throughout the entire length of the study. ResultsBoth nutritional approaches were effective in terms of reducing body fat mass. The HCLF group achieved greater skeletal muscle hypertrophy. Significant decreases in body circumferences, especially in the abdominal area, were observed for both dietary approaches. Maximal strength significantly increased in the HCLF group and decreased in the LCHF group. ConclusionHolistic analysis of the results led to the conclusion that both dietary approaches may elicit positive adaptations in body composition. The two approaches constitute useful alternatives for both recreational exercisers and physique athletes with body composition goals.

Vitamin D3 mitigates type 2 diabetes induced by a high carbohydrate-high fat diet in rats: Role of the purinergic system

This study evaluated the effect of vitamin D3 (VIT D3) supplementation on the enzymatic activities and density of ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5-nucleotidase (E-5′-NT), adenosine deaminase (ADA), as well as the density of P2 × 7R, P2Y12R, A1R, A2AR receptors, IL-1β, and oxidative parameters in type 2 diabetic rats. Forty male Wistar rats were fed a high carbohydrate-high fat diet (HCHFD) and received an intraperitoneal injection containing a single dose of streptozotocin (STZ, 35 mg/kg). Animals were divided into four groups: 1) control; 2) control/VIT D3 12 µg/kg; 3) diabetic; and 4) diabetic/VIT D3 12 µg/kg. Results show that VIT D3 reduced blood glucose, ATP hydrolysis, ADA activity, P2Y12R density (platelets), as well as ATP, ADP, and AMP hydrolysis and ADA activity (synaptosomes). Moreover, VIT D3 increased insulin levels and AMP hydrolysis (platelets) and improved antioxidant defense. Therefore, we suggest that VIT D3 treatment modulates hyperglycemia-induced changes via purinergic enzymes and receptor expression, consequently attenuating insulin homeostasis dysregulation in the diabetic state.

RETRACTED: Astrocyte response to melatonin treatment in rats under high-carbohydrate high-fat diet

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the Editor-in-Chief.Following concerns raised by an anonymous reader regarding possible image manipulation in Figure 3, the journal conducted a thorough investigation. The corresponding author, Dr. Hosseini, acknowledged the image in question was manipulated in error and requested a corrigendum and a revised figure be submitted for consideration. After careful consideration and consultation with the board, the Editor-in-Chief determined that the explanation did not satisfactorily address the concerns presented and a retraction is warranted.The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

Influence of chronic immobilization stress on vitamin status in rats fed different diets

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.

A lipidomic and metabolomic signature of a very low-carbohydrate high-fat diet and high-intensity interval training: an additional analysis of a randomized controlled clinical trial

IntroductionRegular physical activity and dietary variety are modifiable and influential factors of health outcomes. However, the cumulative effects of these behaviors are not well understood. Metabolomics may have a promising research potential to extend our knowledge and use it in the attempts to find a long-term and sustainable personalized approach in exercise and diet recommendations.ObjectiveThe main aim was to investigate the effect of the 12 week very low carbohydrate high fat (VLCHF) diet and high-intensity interval training (HIIT) on lipidomic and metabolomic profiles in individuals with overweight and obesity.MethodsThe participants (N = 91) were randomly allocated to HIIT (N = 22), VLCHF (N = 25), VLCHF + HIIT (N = 25) or control (N = 19) groups for 12 weeks. Fasting plasma samples were collected before the intervention and after 4, 8 and 12 weeks. The samples were then subjected to untargeted lipidomic and metabolomic analyses using reversed phase ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry.ResultsThe VLCHF diet affected plasma lipids considerably while the effect of HIIT was unremarkable. Already after 4 weeks of intervention substantial changes of plasma lipids were found in both VLCHF diet groups. The changes persisted throughout the entire 12 weeks of the VLCHF diet. Specifically, acyl carnitines, plasmalogens, fatty acyl esters of hydroxy fatty acid, sphingomyelin, ceramides, cholesterol esters, fatty acids and 4-hydroxybutyric were identified as lipid families that increased in the VLCHF diet groups whereas lipid families of triglycerides and glycerophospholipids decreased. Additionally, metabolomic analysis showed a decrease of theobromine.ConclusionsThis study deciphers the specific responses to a VLCHF diet, HIIT and their combination by analysing untargeted lipidomic and metabolomic profile. VLCHF diet caused divergent changes of plasma lipids and other metabolites when compared to the exercise and control group which may contribute to a better understanding of metabolic changes and the appraisal of VLCHF diet benefits and harms.Clinical Trial Registry numberNCT03934476, registered 1st May 2019 https://clinicaltrials.gov/ct2/show/NCT03934476?term=NCT03934476&draw=2&rank=1.

Momordica balsamina improves glucose handling in a diet-induced prediabetic rat model

Prolonged exposure to high energy diets has been implicated in the development of pre-diabetes, a long-lasting condition that precedes type 2 diabetes mellitus (T2DM). A combination of pharmacological treatment and dietary interventions are recommended to prevent the progression of pre-diabetes to T2DM. However, poor patient compliance leads to negligence of the dietary intervention and thus reduced drug efficiency. Momordica balsamina (MB) has been reported to possess anti-diabetic effects in type 1 diabetic rats. However, the effects of this medicinal plant in conjunction with dietary intervention on pre-diabetes have not yet been established. Consequently, this study sought to evaluate the effects of MB on glucose homeostasis in a diet-induced pre-diabetes rat model in the presence and absence of dietary intervention. Pre-diabetes was induced on male Sprague Dawley rats by a high fat high carbohydrate (HFHC) diet for a period of 20 weeks. Pre-diabetic male Sprague Dawley rats were treated with MB (250 mg/kg p.o.) in both the presence and absence of dietary intervention once a day every third day for a period of 12 weeks. The administration of MB with and without dietary intervention resulted in significantly improved glucose homeostasis through reduced caloric intake, body weights, with reduced plasma ghrelin concentration and glycated hemoglobin by comparison to the pre-diabetic control. MB administration also improved insulin sensitivity as evidenced by the expression of glucose transporter 4 (GLUT 4) and glycogen synthase on the prediabetic treated animals. These results suggest that MB has the potential to be used to manage pre-diabetes and prevent the progression to overt type 2 diabetes as it demonstrated the ability to restore glucose homeostasis even in the absence of dietary and lifestyle intervention.

Metabolic syndrome: comparison of three diet-induced experimental models

The high-fat (HF) diets can be used to generate a valid rodent model for metabolic syndrome (METS). The aim of this study was to compare three different diets, namely a high-fat, high-carbohydrate diet (HF-HCD), a high-fat lard-based diet (HFD), and a cafeteria diet (CFD), in terms of the ability to induce METS. The next step was to characterize the syndrome according to the biochemical and histopathological changes in the liver and pancreas, and to determine the optimal animal model. As a result, all diets disturbed significantly the serum biochemical parameters. HF-HCD and CFD increased the uric acid levels and reduced the weight gain in comparison with the standard chow diet (SCD) and HFD. The HFD and CFD induced the highest fasting glycemia levels. Although the animals fed with HF-HCD had the lowest body weight, the most serious histopathological changes in the pancreas, hypertension, and oxidative stress were noted in them.

Cholesterol Exacerbates the Pathophysiology of Non-Alcoholic Steatohepatitis by Upregulating Hypoxia-Inducible Factor 1 and Modulating Microcirculatory Dysfunction.

Cholesterol is a pivotal lipotoxic molecule that contributes to the progression of Non-Alcoholic Steatohepatitis NASH). Additionally, microcirculatory changes are critical components of Non-Alcoholic Fatty Liver Disease (NAFLD) pathogenesis. This study aimed to investigate the role of cholesterol as an insult that modulates microcirculatory damage in NAFLD and the underlying mechanisms. The experimental model was established in male C57BL/6 mice fed a high-fat high-carbohydrate (HFHC) diet for 39 weeks. Between weeks 31-39, 2% cholesterol was added to the HFHC diet in a subgroup of mice. Leukocyte recruitment and hepatic stellate cells (HSC) activation in microcirculation were assessed using intravital microscopy. The hepatic microvascular blood flow (HMBF) was measured using laser speckle flowmetry. High cholesterol levels exacerbated hepatomegaly, hepatic steatosis, inflammation, fibrosis, and leukocyte recruitment compared to the HFHC group. In addition, cholesterol decreased the HMBF-cholesterol-induced activation of HSC and increased HIF1A expression in the liver. Furthermore, cholesterol promoted a pro-inflammatory cytokine profile with a Th1-type immune response (IFN-γ/IL-4). These findings suggest cholesterol exacerbates NAFLD progression through microcirculatory dysfunction and HIF1A upregulation through hypoxia and inflammation. This study highlights the importance of cholesterol-induced lipotoxicity, which causes microcirculatory dysfunction associated with NAFLD pathology, thus reinforcing the potential of lipotoxicity and microcirculation as therapeutic targets for NAFLD.

Maca roots: A potential therapeutic in the management of metabolic disorders through the modulation of metabolic biochemical markers in rats fed high-fat high-carbohydrate diet

Ethnopharmacological relevanceMaca root (Lepidium meyenii Walp.) is a Peruvian plant of the Brassicaceae family. Maca roots are popular food supplements used to treat a variety of ailments described traditionally as enhancing metabolic and health conditions. Aim of the studyMetabolic syndrome (MetS) has been the real scourge globally, affecting more than one-fourth of the global population. MetS causes the development of multi-organ illnesses, including altered blood cholesterol and sugar levels, oxidative stress, and hypertension. This study evaluated maca root total methanolic extract (MTE) as a potential nutraceutical to manage the complications of MetS. Materials and methodsAfter the first 4 weeks of a high-fat high-carbohydrate diet (HFCD), streptozotocin (STZ) was injected in Wistar rats to induce the MetS model. Animals were treated orally with MTE at 100 mg/kg and 300 mg/kg for 4 weeks compared to metformin at 200 mg/kg after confirmation of diabetes. ResultsOne month of MTE supplementation in HFCD-fed rats remarkably decreased the elevation of blood glucose and lipids, improved liver function and insulin resistance, additionally it successfully restored the state of inflammatory and oxidative stress. The extract was standardized to contain total phenolics equal to 24.45 ± 0.96 μg Gallic acid/mg extract. ConclusionsOur findings suggest that MTE improves MetS by reducing hyperglycemia, hyperlipidemia, inflammation, and oxidative stress. While also improving beta cell secretory functions, implying that MTE could be used as a balancing drug in the prevention and treatment of metabolic abnormalities linked to type 2 diabetes.

Investigating the Association Between Diet-Induced "Leaky Gut" and the Development of Prediabetes.

Chronic consumption of a high-calorie diet compromises the gut microbiota and the integrity of the intestinal wall, which causes translocation of bacterial lipopolysaccharides (LPS) into the blood. This elicits the secretion of pro-inflammatory cytokines, resulting in inflammation. However, how a high-fat high carbohydrate diet affects intestinal permeability and its possible role in the development of prediabetes have not been investigated. This study investigated the effects of HFHC diet-induced prediabetes on gut microbiota and intestinal permeability in male Sprague Dawley rats. The animals were randomly assigned into the non-prediabetic (NPD) and diet-induced prediabetic (PD) groups (n=6) for 20 weeks. Then, the fecal samples were analyzed to measure the gut microbiota level of Firmicutes, Bacteroidetes, and Proteobacteria in both animal groups. Blood glucose, plasma insulin, serum zonulin, plasma LPS, soluble CD14, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and intestinal fatty-acid binding protein (IFABP) concentrations were measured. The PD group had a reduction in the Firmicutes and an increase in Bacteroidetes and Proteobacteria levels compared to those in the NPD group. Blood glucose, insulin concentration, serum zonulin, and plasma sCD14 concentrations in the PD group increased significantly, while plasma LPS concentrations were similar to the NPD group. Concentrations of plasma TNF-α, IL-6, CRP, and IFABP, an intracellular protein expressed in the intestine, increased in PD compared to the NPD group. the study results cumulatively suggest that chronic consumption of the HFHC diet may be associated with the dysregulation of gut microbiota, leading to increased intestinal permeability.

Assessment of melatonin's therapeutic effectiveness against hepatic steatosis induced by a high-carbohydrate high-fat diet in rats.

Several studies have demonstrated the protective effects of melatonin against metabolic diseases, such as liver steatosis. However, its therapeutic effects have received less scrutiny. The present study aimed to explore melatonin's therapeutic effectiveness in treating non-alcoholic fatty liver disease (NAFLD) induced by a high-carbohydrate high-fat (HCHF) diet in rats. The NAFLD was developed in male Wistar rats using an HCHF diet for 8 weeks. Afterward, they were given melatonin orally for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, along with the HCHF diet. In addition, six age-matched healthy rats received the highest dose of melatonin (30 mg/kg) for the same duration. Rats on the HCHF diet exhibited obesity, dyslipidemia, hyperglycemia, glucose intolerance, insulin resistance, inflammation, oxidative stress, and liver injury (steatosis). Melatonin treatment at 10 mg/kg and 30 mg/kg reduced body weight, adiposity index, oxidative damage, and inflammation but did not affect impaired glucose metabolism induced by the HCHF diet. Meanwhile, the highest dose of melatonin (30 mg/kg) reduced the liver steatosis index in HCHF rats but caused mild liver damage in healthy rats. In conclusion, using melatonin demonstrated positive outcomes in treating NAFLD induced by the HCHF diet in rats, with no noteworthy effects observed in healthy rats. A moderate dosage of 10 mg/kg of melatonin proved to be a safer and more efficient method for reducing HCHF diet-induced NAFLD in rats. Higher melatonin doses should be cautiously administered due to potential disruptions in lipid metabolism and the risk of liver complications.

Association between Altered Thyroid Function and Prediabetes in Diet-Induced Prediabetic Male Sprague Dawley Rats

There is a correlation between the existence of type 2 diabetes mellitus (T2DM) and the development of thyroid disorders. Prediabetes is a progressive state of moderate insulin resistance that often precedes the onset of T2DM. However, the association between prediabetes and thyroid function is unknown. This study assessed changes in markers of thyroid function in diet-induced prediabetes. Twelve male Sprague Dawley rats (n = 12) were randomly assigned into two groups. Rats in the non-prediabetic (NPD) group were fed a standard rat diet, while rats in the prediabetic (PD) were fed a high-fat high-carbohydrate diet for 20 weeks to induce prediabetes. Thereafter, fasting blood glucose levels were measured. Plasma samples were assessed for triiodothyronine (T3), thyroxine (T4), thyroxine peroxidase (TPO) antibody, insulin, and glycated hemoglobin (HbA1c) concentrations. The elevated blood glucose, HbA1c, and plasma insulin levels coincided with increased T3 and reduced T4 levels in the PD group when compared to the NPD group. There was also an increase in the concentration of TPO antibodies in the PD group. Additionally, there was a significant correlation between the thyroid hormone concentrations and HbA1c levels. In conclusion, these results indicated that there is a positive association between thyroid dysfunction and diet-induced prediabetes in rats.

The Polyherbal Functional Ingredient Containing Ginger, Chinese Date, and Wood Ear Mushroom Protects against Dementia following Metabolic Syndrome.

The anti-dementia effect following ischemic stroke with metabolic syndrome (MetS) of the polyherbal functional ingredient comprising ginger, Chinese date, and wood ear mushroom (GCJ) was hypothesized due to its neuroprotective effect against stroke. This study was performed to test this hypothesis and to explore the underlying mechanism. Male Wistar rats weighing 180-220 g were induced metabolic syndrome (MetS) with a 16-week high-carbohydrate high-fat diet (HCHF) feeding. The rats with MetS characteristics were orally administered GCJ at various doses (GCJ100, GCJ200, and GCJ300 mg kg-1 BW) 21 days pre-induction and 21 days post-induction of reperfusion injury (I/R) at the right middle cerebral artery (MCAO). Memory was evaluated every 7 days during the study period. At the end of the study, neuron density, AChE activity, and the expressions of eNOS, BDNF, and pERK/ERK in the prefrontal cortex, and hippocampus were also determined. MetS rats with GCJ treatment improved memory impairment, enhanced neuron density, and increased the expressions of eNOS, BDNF, and pERK/ERK but suppressed AChE in both areas. Therefore, the anti-dementia effect following ischemic stroke with metabolic syndrome of GCJ may involve the improvement of AChE, eNOS, BDNF, pERK/ERK, and neural plasticity. However, this required confirmation by clinical study.

The Effect of Semi-Synthetic and High-Fat High-Carbohydrate Diets Containing Cholesterol on Lipid and Cholesterol Metabolism in Male Wistar Rats.

The choice of an optimal biological model of exogenous hypercholesterolemia is necessary for correct assessment of the cholesterol-lowering properties of bioactive substances and specialized food products and for validity of the experimental results. We studied the effects of cholesterol consumption in the composition of the standard semi-synthetic diet and high-fat high-carbohydrate diet for more than 3 months on lipid and cholesterol metabolism in male Wistar rats. Our findings suggest that cholesterol consumption in both diets led to a significant impairment of lipid and cholesterol metabolism, as well as an increase in insulin resistance in rats.

Metabolism effector links in diet-induced and genetically-based obesity: A full-transcriptome study of liver tissue in experimental models in rodents

Background. When developing methods for personalized diet therapy of obesity, an urgent task is to study the molecular genetics features of the obesity pathogenesis using in vivo experimental models in laboratory animals.The aim. To determine metabolism effector links in obesity based on a comparative analysis of full-transcriptome profiles of the liver tissue of mice and rats of various strains.Materials and methods. We carried out a comparative analysis of the changes in liver transcriptome in rats and mice fed with diets of excessive energy value and exerting lipogenic effect. Data of full-transcriptome profiling using DNA microarray technology have been presented previously in 8 publications. Results. In three strains of mice treated with a high-carbohydrate high-fat diet (HCHFD), a significant differential expression (DE) of 1849 genes was revealed, of which 74 genes responded jointly in at least two groups of animals. In Wistar and Zuckerfa rats, 2109 genes responded to the consumption of HCHFD, of which 242 genes responded jointly in two groups of animals. For rodents different in genetic predisposition to the development of diet-induced obesity, the groups of genes that responded with the opposite sign of DE (depending on the genotype) in reaction to the consumption of HCHFD were identified. Bioinformatical analysis allowed establishing the presence of 43 metabolic pathways, which are targeted for the applied experimental diets exposure, in rats and 77 pathways – in mice. Four of these pathways – the pathway of retinoid metabolism, PPAR signaling pathway associated with it the previous one, xenobiotics metabolism and drugs metabolism mediated by cytochrome P450 system – responded in all groups of animals (except for female mice). The importance of the expression of Tat gene encoding tyrosine aminotransferase in the modulation of biogenic amines synthesis in diet-induced obesity was shown, which may represent a new neurometabolic regulatory function of the liver in response to the consumption of high-calorie diets. Conclusion. The analysis of the results of full-transcriptome studies showed that within each studied species (Rattus rattus and Mus domesticus) and animal sex, a number of genetic variants with a greater or lesser predisposition to the development of diet-induced obesity phenotype can be identified; and at the same time, within these variants, there is a largely similar pattern in the response of metabolism effector links to hypercaloric dietary intake. This pattern creates new prospects for translating the results of transcriptomic and metabolomic studies of laboratory animals into clinical practice in order to substantiate new approaches to personalized diet therapy of alimentary dependent diseases in patients with different genetic predisposition to obesity.

Animal-based ketogenic diet puts severe anorexia nervosa into multi-year remission: A case series

Background: Anorexia nervosa is a devastating condition that increases risk of death over five-fold and is associated with a high rate of relapse. Considering the growing field of metabolic psychiatry, anorexia can be framed as a ‘metabolic-psychiatric’ condition that may benefit from treatment with metabolic health interventions with neuromodulatory properties. Ketogenic diets, very low carbohydrate high-fat diets, are one such neuromodulatory intervention with a long history of use in epilepsy and more recently in other systemic, neurological and mental health conditions.Aim: To describe clinical cases that highlight the potential of ketogenic diets in the treatment of anorexia and the need for further research.Setting: Patient interviews were conducted via telemedicine.Methods: Medical interviews and chart reviews were conducted with three patients with severe anorexia. Written informed consent was provided by all participants.Results: Patients with anorexia, body mass index (BMI) nadirs of 10.7 kg/m2, 13.0 kg/m2 and 11.8kg/m2 and refractory to standard of care therapy, each achieved remission of between 1–5 years to date on a high-fat animal-based ketogenic diet. Patients exhibited not only improvements in weight, with weight gain of over 20 kg each, but also diminution of anxiety and overall enhanced mental well-being.Conclusion: These cases suggest a ketogenic diet may be useful for some patients with anorexia. Further research is needed.Contribution: This case series is the first to document treatment of anorexia with unimodal ketogenic diet intervention and raises provocative questions about the role of this neuromodulatory dietary treatment for patients with anorexia, as well as the neurometabolic nature of the disease itself.