High-fat High-carbohydrate Diet Research Articles

Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress.

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product–receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat–high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters.

Effect of Kelulut honey supplementation on bone health in male rats on high-carbohydrate high-fat diet


 
 
 
 Purpose: To determine the effects of Kelulut honey (KH) on the bone health of rats with metabolic syndrome.
 Methods: Male Wistar rats were randomised into normal control and metabolic syndrome is fed with a diet enriched with carbohydrate and fat. The rats in the metabolic syndrome arm were further assigned into the negative control group and honey group supplemented orally with Kelulut honey (1g/kg) daily for eight weeks. After the rats were sacrificed, the trabecular and cortical micro-architecture of the harvested femur was analysed using X-ray micro-computed tomography, while histomorphometric method was used to determine bone cell indices. Femoral biomechanical properties were analysed using a universal mechanical tester.
 Results: Total cross-sectional area, osteoid surface and volume, displacement and strain reduced significantly, while eroded surface increased significantly in the rats with metabolic syndrome than the normal rats (p < 0.05). The honey group showed a significant reduction in osteoclast surface than the normal healthy control (p < 0.05). Other skeletal parameters did not show a significant intergroup difference.
 Conclusion: Metabolic syndrome is harmful to bone health and honey has limited effects in reversing these negative effects.
 
 
 

High-fat/high-carbohydrate-diet short- and middle-term effects on gerbil adrenal zona fasciculata histology

The adrenals synthesize many hormones involved in the regulation and maintenance of homeostasis. To understand the pathophysiological changes during the development of obesity, a histological study of the adrenal was performed in gerbils receiving a high-fat/high-carbohydrate-diet (HFC) for 8 or 12 weeks. Compared to the controls, the HFC diet increased body weight. Our results reveal significant weight and structural changes in the HFC group’s adrenal glands (confirmed by gray level co-occurrence matrix texture and fractal analysis), disorganization of zona fasciculata (8 weeks) and hyperplasia and peri-capillary fibrosis (12 weeks). In conclusion, these results show that an HFC induces time-dependent structural lesions of the adrenals in gerbils, which could be a sign of chronic adaptation of these glands.

Physiological and biochemical evaluation of the effectiveness of a new food ingredient - blueberry polyphenol concentrate

Extracts from bilberry leaves and blueberries containing a wide range of biologically active compounds, including polyphenols, are of particular interest due to their antioxidant, hypoglycemic and hypolipidemic properties. In this regard, The aim of this research was to investigate in vivo the effect of a concentrate of blueberrie polyphenolic compounds with buckwheat flour on some physiological and biochemical parameters in C57Bl/6 mice with impaired carbohydrate and lipid metabolism induced by the consumption of a high fat high carbohydrate (HFHC) diet. Material and methods. The polyphenol concentrate was obtained by sorption of blueberry extract on grinded buckwheat flour. Total polyphenol content was determined by Folin-Ciocalteu method, profiles of anthocyanins, flavonoids and easily digested carbohydrates were determined by HPLC. An in vivo experiment was carried out using 84 male mice C57Bl/6 for 109 days. Animals were divided into 3 groups: control fed standard semisynthetic diet, control treated with HFHC diet and experimental group treated with HFHC diet with addition of blueberry polyphenol concentrate (60 mg-eq. of gallic acid/kg body weight). Food intake, body weight gain and fasting blood glucose levels were measured during the experiment. Grip strength of the front paws of the animals was measured weekly. Oral glucose tolerance and insulin resistance tests were carried out twice. Common physiological tests (Elevated Plus Maze and Passive Avoidance Test) were used to assess the anxiety and memory of animals. Glycated hemoglobin level was determined in blood, plasma was collected for leptin and insulin level determination. The hepatic levels of triglycerides and cholesterol were assessed. Results. The concentrate of polyphenols extracted from blueberries and sorbed on grinded buckwheat flour was obtained under conditions that made it possible to exclude the sorption of easily digested carbohydrates - glucose, fructose and sucrose on the flour. The total concentrate content of polyphenols was 65.5±0.7 mg-eq. gallic acid/g, anthocyanins - 27.3±2.7 mg/g, flavonoids - 1.2±0.1 mg/g. The consumption of the concentrate by C57Bl/6 male mice with carbohydrate and lipid metabolism disorders induced by a HFHC diet had a significant (p<0.05) hypoglycemic and hypolipidemic effect, reducing the area under the curve in the insulin resistance test by 5.7% and decreasing the insulin and leptin levels by 31.3 and 15.9%, respectively (relative to the animals of comparison group fed HFHC diet). The consumption of the concentrate had a significant (p<0.05) anxiolytic effect, reducing the anxiety of animals by 2.2 times, as determined in the Elevated Plus Maze test. Conclusion. The results of the study indicate the prospects for using the developed blueberry polyphenol concentrate adsorbed on buckwheat flour as part of specialized foods for the prevention of such alimentary dependent diseases as metabolic syndrome, obesity, and diabetes mellitus.

High Vaccenic Acid Content in Beef Fat Attenuates High Fat and High Carbohydrate Western Diet Induced Changes in Lipid Metabolism and Gut Microbiota in Pigs.

High-fat diets (HFD) have been shown to induce substantial shifts in intestinal microbial community composition and activity which are associated with adverse metabolic outcomes. Furthermore, changes in microbial composition are affected by fatty acid composition; saturated, monounsaturated (MUFA), and industrial trans fats (iTFA) adversely affect microbial diversity while polyunsaturated fats (PUFA) have been shown to have neutral effects. The effects of naturally occurring trans fats on gut microbial composition are unknown. Vaccenic acid (VA) is the most abundant naturally occurring trans fat (abundant in meat and dairy), can be elevated by altering a cow’s diet, and has been shown to have hypolipidemic effects. The aim of this study was to determine how variations of VA content in beef fat affect gut microbial composition, insulin resistance, and lipid metabolism in pigs. Low birth weight (LBW) and control pigs were fed a control or high-fat, high-carbohydrate (HFHC) diet supplemented with beef fat containing either high or low VA levels for 7 weeks. An adapted modified oral glucose tolerance test and fat challenge test were performed at 9 weeks of age following implantation of jugular catheters. Impacts on microbial composition were assessed using 16S rRNA gene amplicon sequencing. The HFHC diet containing beef fat rich in VA had a mild insulin sensitizing effect (p < 0.05, slope of curve), increased plasma HDL cholesterol (p < 0.05, +28%), reduced postprandial plasma TG (p < 0.05), and showed protection from HFHC-induced changes to gut microbial composition in LBW pigs as compared to HFHC diet containing standard beef fat. This is the first study to show effects of natural trans fats on gut dysbiosis; further studies are needed to elucidate mechanisms.

Hepatocyte-specific deletion of adipose triglyceride lipase (adipose triglyceride lipase/patatin-like phospholipase domain containing 2) ameliorates dietary induced steatohepatitis in mice.

Increased fatty acid (FA) flux from adipose tissue to the liver contributes to the development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting adipose triglyceride lipase (ATGL)/patatin-like phospholipase domain containing 2 (PNPLA2), the main enzyme driving lipolysis, may attenuate steatohepatitis. Hepatocyte-specific ATGL knockout (ATGL LKO) mice were challenged with methionine-choline-deficient (MCD) or high-fat high-carbohydrate (HFHC) diet. Serum biochemistry, hepatic lipid content and liver histology were assessed. Mechanistically, hepatic gene and protein expression of lipid metabolism, inflammation, fibrosis, apoptosis, and endoplasmic reticulum (ER) stress markers were investigated. DNA binding activity for peroxisome proliferator-activated receptor (PPAR) α and PPARδ was measured. After short hairpin RNA-mediated ATGL knockdown, HepG2 cells were treated with lipopolysaccharide (LPS) or oleic acid:palmitic acid 2:1 (OP21) to explore the direct role of ATGL in inflammation in vitro. On MCD and HFHC challenge, ATGL LKO mice showed reduced PPARα and increased PPARδ DNA binding activity when compared with challenged wild-type (WT) mice. Despite histologically and biochemically pronounced hepatic steatosis, dietary-challenged ATGL LKO mice showed lower hepatic inflammation, reflected by the reduced number of Galectin3/MAC-2 and myeloperoxidase-positive cells and low mRNA expression levels of inflammatory markers (such as IL-1β and F4/80) when compared with WT mice. In line with this, protein levels of the ER stress markers protein kinase R-like endoplasmic reticulum kinase and inositol-requiring enzyme 1α were reduced in ATGL LKO mice fed with MCD diet. Accordingly, pretreatment of LPS-treated HepG2 cells with the PPARδ agonist GW0742 suppressed mRNA expression of inflammatory markers. Additionally, ATGL knockdown in HepG2 cells attenuated LPS/OP21-induced expression of proinflammatory cytokines and chemokines such as chemokine (C-X-C motif) ligand 5, chemokine (C-C motif) ligand (Ccl) 2, and Ccl5. Low hepatic lipolysis and increased PPARδ activity in ATGL/PNPLA2 deficiency may counteract hepatic inflammation and ER stress despite increased steatosis. Therefore, lowering hepatocyte lipolysis through ATGL inhibition represents a promising therapeutic strategy for the treatment of steatohepatitis.

Comprehensive assessment of the effectiveness of l-carnitine and transresveratrol in rats with diet-induced obesity

ObjectivesTransresveratrol (Res) and l-carnitine (l-Car) are proposed to alleviate metabolic and immune disorders and increase physical activity in obese individuals. This study aims to estimate the effect of Res and l-Car in rats with diet-induced obesity. MethodsMale Wistar rats were fed a diet with excess fat and fructose (high-fat high-carbohydrate diet [HFCD]) supplemented with Res and l-Car at doses of 25 and 300 mg/kg of body weight, respectively, for 63 d. An assessment of grip strength, behavioral reactions, as well as biochemical, morphological, and immunological parameters, was performed. ResultsRes supplementation did not affect energy consumption, but l-Car increased when animals had free access to feed. Body weight gains were the highest in animals fed the HFCD, lowest in rats receiving the control balanced diet, and intermediate in animals receiving Res and l-Car. Feeding with Res and l-Car canceled the decrease in long-term memory in rats fed the HFCD, as well as reduced anxiety and increased mobility. With both supplements, bilirubin, triglycerides, and low-density lipoprotein levels in the blood plasma returned to normal values, but only l-Car increased the ratio of aspartic and alanine transaminases. In addition, l-Car lowered the levels of leptin and ghrelin and increased transforming growth factor beta 1 in the blood plasma, and consumption of Res was accompanied by a decrease in interleukin-17A and increase in interferon gamma in spleen lysates. Moreover, l-Car reduced the number of cells with lipid inclusions in the liver. ConclusionsThe consumption of Res and l-Car leads to a significant reduction in dyslipidemia and inflammation with potentially favorable changes in behavioral responses.

The role of soluble TNF in mediating immune and metabolic alterations in a mouse model of amyloid-beta pathology.

Insulin resistance (IR) and systemic inflammation are risk factors for Alzheimer's disease (AD); however, the molecular and signaling mechanisms underlying this relationship are not well understood. Elevated plasma cytokine levels are associated with increased risk for both AD and IR. The cytokine tumor necrosis factor (TNF) is a major driver of inflammation and is implicated in IR and neurodegeneration. Here, we hypothesize that soluble TNF (solTNF) drives metabolic and immune alterations in the CNS and periphery that promote IR, thereby increasing the risk for AD pathologies. To investigate this hypothesis, 2-month old female 5xFAD mice were fed a high-fat high-carbohydrate diet (HFHC) or a control diet (CD) for 8 weeks. After 1 month, the brain-permeant solTNF inhibitor XPro1595 or a brain-impermeant pan (sol and membrane-bound) TNF inhibitor Etanercept or saline were dosed twice weekly for 4 weeks. Plasma, adipose tissue, and gut were collected for evaluation of IR, metabolic and immune parameters. Molecular markers of insulin signaling, oxidative stress, mitochondrial impairment and inflammation were assessed in relevant brain regions (hippocampus, hypothalamus and cortex). Our preliminary data demonstrate that HFHC-fed 5XFAD mice exhibit increased body weight gain compared to CD groups. Ectopic lipid deposition, as measured by gonadal fat pad and liver volumes, was significantly increased, concurrent to anatomical indicators of intestinal inflammation, including shortened small intestine and colon. HFHC diet promoted systemic inflammation, as measured by increases in the classical pro-inflammatory cytokines IL-6 and TNF. Further, plasma LCN2, a downstream TNF inflammatory molecule associated with insulin insensitivity, hippocampal alterations, and previously observed to be increased in AD patients, was also significantly increased. Ongoing assessments of mRNA and protein expression of insulin signaling and inflammation in the hippocampus and cortex will determine additional effects of TNF in central insulin impairment and AD pathogenesis and will be presented and integrated into the overall findings. Together, these data suggest HFHC diet disrupts peripheral immune and metabolic parameters in the 5XFAD animal model of AD-like pathology, thereby triggering neuroinflammation and insulin insensitivity, conditions which have been implicated in significantly increasing the risk for development of AD in humans.

What Is the Impact of Energy Expenditure on Energy Intake?

Coupling energy intake (EI) to increases in energy expenditure (EE) may be adaptively, compensatorily, or maladaptively leading to weight gain. This narrative review examines if functioning of the homeostatic responses depends on the type of physiological perturbations in EE (e.g., due to exercise, sleep, temperature, or growth), or if it is influenced by protein intake, or the extent, duration, timing, and frequency of EE. As different measures to increase EE could convey discrepant neuronal or humoral signals that help to control food intake, the coupling of EI to EE could be tight or loose, which implies that some ways to increase EE may have advantages for body weight regulation. Exercise, physical activity, heat exposure, and a high protein intake favor weight loss, whereas an increase in EE due to cold exposure or sleep loss likely contributes to an overcompensation of EI, especially in vulnerable thrifty phenotypes, as well as under obesogenic environmental conditions, such as energy dense high fat—high carbohydrate diets. Irrespective of the type of EE, transient elevations in the metabolic rate seem to be general risk factors for weight gain, because a subsequent decrease in energy requirement is not compensated by an adequate adaptation of appetite and EI.

High carbohydrate high fat diet causes arterial hypertension and histological changes in the aortic wall in aged rats: The involvement of connective tissue growth factors and fibronectin

BackgroundAge and diabetes are risk factors for arterial hypertension. However, the relationship between age, connective tissue growth factors, vascular aging and arterial hypertension while on a the high-carbohydrate high-fat diet (HCHFD) remains poorly understood. PurposeTo estimate the relationship between humoral factors, the morphological changes of aorta and impaired blood pressure regulation under the influence of age and a HCHFD. MethodsA study was carried out in male Wistar rats, which were divided into the following groups: 1st (n = 15) - naive young rats; 2nd (n = 15) – young rats, exposed to HCHFD; 3rd (n = 14) – naive old rats; 4th (n = 12) - old rats exposed to HCHFD. The age of old rats was 540 days, and young rats 150 days at the end of the diet. HCHFD contained proteins 16%, fats 21%, carbohydrates 46%, including 17% fructose, 0.125% cholesterol, 90 days. Blood pressure and body weight were measured weekly, carbohydrate metabolism, histological signs of changes in the aorta, serum transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), fibronectin, and endothelin-1 levels were determined one week after the onset of diet. ResultsThe severity of arterial hypertension and its histological signs in the aortic wall was found to be most pronounced in elderly rats kept on a HCHFD. In young rats kept on a HCHFD, arterial hypertension was transient. An increase in systolic blood pressure has a positive correlation with the degree of obesity, serum fibronectin, and endothelin-1 content, and impaired carbohydrate metabolism. The rise in diastolic blood pressure has a positive correlation with the serum CTGF, endothelin-1, fibronectin levels and aortic wall thickness, and impaired carbohydrate metabolism. A rise in the serum concentration of fibronectin was also associated with increased endothelin-1, TGFβ and CTGF serum levels. ConclusionThis study indicated that an increase in blood pressure in old rats with a high-carbohydrate high-fat diet is due to a disturbance of a structure of the vascular wall, the release of fibronectin, which can occur under the influence of carbohydrate metabolism disorders, endothelin-1, TGFβ and CTGF.

Non-hematopoietic IL-4R\u03b1 expression contributes to fructose-driven obesity and metabolic sequelae

ObjectiveThe risks of excess sugar intake in addition to high-fat diet consumption on immunopathogenesis of obesity-associated metabolic diseases are poorly defined. Interleukin-4 (IL-4) and IL-13 signaling via IL-4Rα regulates adipose tissue lipolysis, insulin sensitivity, and liver fibrosis in obesity. However, the contribution of IL-4Rα to sugar rich diet-driven obesity and metabolic sequelae remains unknown.MethodsWT, IL-4Rα-deficient (IL-4Rα−/−) and STAT6-deficient mice (STAT6−/−) male mice were fed low-fat chow, high fat (HF) or HF plus high carbohydrate (HC/fructose) diet (HF + HC). Analysis included quantification of: (i) body weight, adiposity, energy expenditure, fructose metabolism, fatty acid oxidation/synthesis, glucose dysmetabolism and hepatocellular damage; (ii) the contribution of the hematopoietic or non-hematopoietic IL-4Rα expression; and (iii) the relevance of IL-4Rα downstream canonical STAT6 signaling pathway in this setting.ResultsWe show that IL-4Rα regulated HF + HC diet-driven weight gain, whole body adiposity, adipose tissue inflammatory gene expression, energy expenditure, locomotor activity, glucose metabolism, hepatic steatosis, hepatic inflammatory gene expression and hepatocellular damage. These effects were potentially, and in part, dependent on non-hematopoietic IL-4Rα expression but were independent of direct STAT6 activation. Mechanistically, hepatic ketohexokinase-A and C expression was dependent on IL-4Rα, as it was reduced in IL-4Rα-deficient mice. KHK activity was also affected by HF + HC dietary challenge. Further, reduced expression/activity of KHK in IL-4Rα mice had a significant effect on fatty acid oxidation and fatty acid synthesis pathways.ConclusionOur findings highlight potential contribution of non-hematopoietic IL-4Rα activation of a non-canonical signaling pathway that regulates the HF + HC diet-driven induction of obesity and severity of obesity-associated sequelae.

Proteomic Analysis of Peripheral Blood Mononuclear Cells Following a Single High Fat High Carbohydrate Meal Challenge

ObjectivesAn individual’s ability to adapt to a dynamic environment is termed ‘phenotypic flexibility’ and can be weakened by chronic stress, leading to dysregulation of normal homeostatic processes. A long-term high energy and high fat high carbohydrate (HFHC) diet increases risk of metabolic diseases, however, the acute effect of a single HFHC meal on disturbances in metabolic homeostasis is less understood. In this study, we aimed to characterise the effect of a single HFHC meal on the postprandial proteome of peripheral blood mononuclear cells (PBMCs). MethodsTwelve healthy men (22.7 ± 3.4 years, BMI of 22.2 ± 1.5 kg/m2) were recruited. Participants consumed a HFHC milkshake after fasting overnight. The meal contained 16 g of carbohydrate and 15 g of fat per 100 g and had a total energy content of 64 kJ/kg body weight. PBMCs were collected at fasting, 3 and 6 hours following the meal. The proteome was measured via LC-MS/MS using untargeted label-free quantification. Differentially expressed proteins were identified with a modified paired t test (limma, R v.4.0.3). Gene ontology analysis was performed with ClueGO v2.5.7 in Cytoscape v3.8.2. ResultsAfter filtering to include only high confident proteins consistently detected in each condition, 6007 proteins were identified and included in analysis. Changes in protein expression relative to fasting were observed at 3 hours (143 proteins) and 6 hours (210 proteins) post meal (fold change > ±1.2, p < 0.05). The most highly altered biological processes observed at each timepoint were ‘zymogen activation’ (GO:0,031,638, 31.25% of groups at 3 hours) and ‘ribosome biogenesis’ (GO:0,042,254, 19.15% of groups at 6 hours). ConclusionsThese results reveal adaptations that occur in the PBMC proteome in response to a single HFHC meal. Changes to proenzyme activation shows a general response in PBMCs to meal-induced changes in the cellular environment, whilst regulation of ribosome synthesis pathways may reflect changes in energy regulation pathways caused by increased nutrient availability. This study characterises the PBMC response in healthy men, and provides a useful reference for future studies that investigate how PBMCs lose the ability to maintain homeostasis following a HFHC meal. Funding SourcesMonash University, Melbourne, Australia

Effects of Tyrosine and Tryptophan Supplements on the Vital Indicators in Mice Differently Prone to Diet-Induced Obesity.

We studied the effects of the addition of large neutral amino acids, such as tyrosine (Tyr) and tryptophan (Trp), in mice DBA/2J and tetrahybrid mice DBCB receiving a high-fat, high-carbohydrate diet (HFCD) for 65 days. The locomotor activity, anxiety, muscle tone, mass of internal organs, liver morphology, adipokines, cytokines, and biochemical indices of animals were assessed. The Tyr supplementation potentiated increased anxiety in EPM and contributed to a muscle tone increase, a decrease in the AST/ALT ratio, and an increase in protein anabolism in both mice strains. Tyr contributed to a decrease in liver fatty degeneration and ALT reduction only in DBCB that were sensitive to the development of obesity. The addition of Trp caused an increase in muscle tone and potentiated an increase in anxiety with age in animals of both genotypes. Trp had toxic effects on the livers of mice, which was manifested in increased fatty degeneration in DBCB, edema, and the appearance of micronuclei in DBA/2J. The main identified effects of Tyr on mice are considered in the light of its modulating effect on the dopamine neurotransmitter metabolism, while for the Trp supplement, effects were presumably associated with the synthesis of its toxic metabolites by representatives of the intestinal microflora.

High carbohydrate high fat diet induces the production of connective tissue growth factors, increased blood pressure, and changes in the aortic wall in aged rats

Age and diabetes are a risk factor for arterial hypertension. In the presented work, the morphological basis of an increase in blood pressure under the influence of a high-carbohydrate high-fat diet in old rats was investigated. It was determined the connective tissue growth factor levels and morphological changes in the aortic wall. A study was carried out in male Wistar rats weighing 350–400 g, 140 day old and rats weighing 530-620 g, 540 day old at the end of research. All procedures conformed to the Directive 2010/63/EU of the European Parliament and FASEB Statement of Principles for the use of Animals in Research and Education. Ethical approval was granted by the Ethical Committee of Research Institute of Cardiology, Tomsk National Research Medical Center. The high carbohydrate high fat diet (HCHFD) consisted from proteins 16%, fats 21%, carbohydrates 46%, including 17% fructose, 0.125% cholesterol, 90 days. Control group rats were fed a standard rat diet. It was found that the severity of arterial hypertension (Fig. 1), histological changes in the aortic wall (Fig. 2), and the level of connective tissue growth factors (TGFbeta, CTGF, fibronectin; Fig. 1) were significantly increased in elderly rats kept on a high-carbohydrate high-fat diet than young animals. In young rats kept on a high-carbohydrate, high-fat diet, arterial hypertension has a transient hypervolumic hallmark and does not cause changes in the aortic wall. The rise in blood pressure has a positive correlation with CTGF and fibronectin content (Fig. 1). These findings indicate that the formation of increased blood pressure in old rats when kept on a high carbohydrate high fat diet is associated with changes in the morphological structure of the aorta and is due to increased production of connective tissue growth factors.

Diet-induced prediabetes: effects of exercise treatment on risk factors for cardiovascular complications

BackgroundAn animal model of prediabetes that has been developed in our laboratory using a high fat high carbohydrate diet and lack of physical activity displays risk factors for cardiovascular complications. The effect of exercise against these risk factors in this animal model remains unknown. Therefore, we evaluated the effect of intermittent and regular exercise treatment on the risk factors for cardiovascular complications in this animal model of prediabetes.MethodsFollowing prediabetes induction, animals were randomly assigned to the following groups (n = 6): non-diabetic, prediabetic, intermittently exercising prediabetic and regularly exercising prediabetic. Exercise exposure was 7 weeks long. Body weight changes, caloric intake, blood glucose, total cholesterol, and triglyceride concentration was measured after 20 and 29 weeks while blood pressure was only measured after 29 weeks. Plasma endothelial nitric oxide synthase, malonaldehyde, glutathione peroxidase, tumour necrosis factor-alpha and C-reactive protein concentration from the heart were measured 2 weeks post-exercise termination (week 30).ResultsWe found increased body weight, caloric intake and mean arterial pressure in the prediabetic group by comparison to the non-prediabetic group. The same trend was observed in blood glucose and triglyceride concentrations. However, all of these parameters were reduced in the intermittently exercising prediabetic and regularly exercising prediabetic groups. This reduction was further accompanied by a decrease in the endothelial nitric oxide synthase, tumour necrosis factor-alpha and C-reactive protein concentration with improved oxidative stress biomarkers.ConclusionsThe progression of pre-diabetes to diabetes is slowed or possibly stopped by exercise (regular or intermittent). Additionally, biomarker profiles indicative of cardiovascular disease in pre-diabetics are improved by exercise.

Greater Loss of Central Adiposity from Low-Carbohydrate versus Low-Fat Diet in Middle-Aged Adults with Overweight and Obesity.

The objective of this study is to determine whether middle-aged adults prescribed a low carbohydrate-high fat (LCHF) or low fat (LF) diet would have greater loss of central fat and to determine whether the insulin resistance (IR) affects intervention response. A total of 50 participants (52.3 ± 10.7 years old; 36.6 ± 7.4 kg/m2 BMI; 82% female) were prescribed either a LCHF diet (n = 32, carbohydrate: protein: fat of 5%:30%:65% without calorie restriction), or LF diet (n = 18, 63%:13–23%: 10–25% with calorie restriction of total energy expenditure—500 kcal) for 15 weeks. Central and regional body composition changes from dual-x-ray absorptiometry and serum measures were compared using paired t-tests and ANCOVA with paired contrasts. IR was defined as homeostatic model assessment (HOMA-IR) > 2.6. Compared to the LF group, the LCHF group lost more android (15.6 ± 11.2% vs. 8.3 ± 8.1%, p < 0.01) and visceral fat (18.5 ± 22.2% vs. 5.1 ± 15.8%, p < 0.05). Those with IR lost more android and visceral fat on the LCHF verses LF group (p < 0.05). Therefore, the clinical prescription to a LCHF diet may be an optimal strategy to reduce disease risk in middle-aged adults, particularly those with IR.

Bioavailability of Omega-3 Fatty Acid In Normal and High Fat High Carbohydrate Diet Induced Animal Model

Bioavailability of Omega-3 Fatty Acid In Normal and High Fat High Carbohydrate Diet Induced Animal Model

The role of pioglitazone in antioxidant, anti-inflammatory, and insulin sensitivity in a high fat-carbohydrate diet-induced rat model of insulin resistance.

We explored the cascade effects of a high fat-carbohydrate diet (HFCD) and pioglitazone (an anti-diabetic therapy used to treat type 2 diabetes mellitus (T2DM)) on lipid profiles, oxidative stress/antioxidant, insulin, and inflammatory biomarkers in a rat model of insulin resistance. Sixty albino rats (80-90 g) were randomly divided into three dietary groups; 1) standard diet; 2) HFCD diet for 12 weeks to induce an in vivo model of insulin resistance; and 3) HFCD diet plus pioglitazone. Blood and tissue samples were taken to assess hepatic function, lipid profiles, oxidative biomarkers, malondialdehyde (MDA) levels, antioxidant defense biomarkers, including reduced glutathione (GSH), superoxide dismutase (SOD), and the inflammatory markers interleukin-6 (IL-6) and tumor necrotic factor (TNF-α). HFCD-fed rats had significantly (P≤0.05) increased serum triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein (LDL), alanine transaminase (ALT), and bilirubin levels, but decreased high-density lipoprotein (HDL) levels compared with the normal group. Moreover, serum leptin, resistin, TNF-α, and IL-6 levels were increased significantly in HFCD animals compared with controls. Similarly, HFCD-induced insulin resistance caused antioxidant and cytokine disturbances, which are important therapy targets for pioglitazone. Importantly, administration of this drug ameliorated these changes, normalized leptin and resistin and inflammatory markers by reducing TNF-α levels. Metabolic cascades of elevated lipid profiles, oxidative stress, insulin, and inflammatory biomarkers are implicated in insulin resistance progression. HFCD induced metabolic cascades comprising hypertriglyceridemia, hyperglycemia, insulin resistance, obesity-associated hormones, and inflammatory biomarkers may be alleviated using pioglitazone.

Liver gene expression in normal and obese rats received resveratrol and L-carnitine

The use of nutraceuticals with anti-inflammatory and hypolipidemic activity in the composition of foods for special dietary uses and dietary supplements is one of the effective methods of dietary therapy of alimentary obesity and related diseases. The aim was to study the effect of the combined intake of resveratrol and L-carnitine (RC) on the expression of genes responsible for the metabolism of carbohydrates, fats and inflammatory reactions in the liver and kidneys of rats in normal conditions and with diet-induced obesity. Material and methods. Male Wistar rats received for 63 days a standard balanced diet or a high-fat-high-carbohydrate diet (HFCD) with an excess of total fat (30%) and fructose (20% solution instead of drinking water), or the same diets supplemented with RC in a low (25 mg/kg body weight as resveratrol and 300 mg/kg as L-carnitine) or high (50 and 600 mg/kg body weight, respectively) doses. The expression of genes (Khk, Gck, Pklr, Acaca, Acacb, Fasn, Scd, Srebf1, Mlxipl, Ppara, Pparg, Actb, Gapdh) in liver cells was studied by the method of real-time reverse transcription polymerase chain reaction (RT-PCR). The distribution of tyrosine aminotransferase (TAT), nuclear factor erythroid 2-related factor 2 (NRF-2) and intercellular adhesion molecule type 2 (ICAM-2) in the liver and kidneys was assessed by confocal laser microscopy and immunohistochemistry. Results. Increased expression of Fasn (fatty acid synthase) in rats treated with high-fat high-carbohydrate diet (HFCD) decreased under RC intake. RC consumption caused a decrease in the number of TAT-, NRF-2- and ICAM-2-positive cells in the liver of rats treated with HFCD, but had the opposite effect in the kidneys. The consumption of RC at the low dose by rats fed HFCD caused changes in the expression profiles of the studied marker genes, indicating a possible hypolipidemic effect. However, observed increased expression of lipogenic genes in the liver and elevated level of NRF-2 and ICAM-2 in kidney against the background of consumption of RC with the standard balanced diet cannot be assessed as unambiguously positive. Conclusion. Thus, possible negative effects caused, most likely, by the interaction of nutraceuticals with various mechanisms of action should be taken into account when developing formulations of dietary supplements and foods for special dietary uses for dietary therapy of obesity.

Influence of the L-carnitine and resveratrol complex on physiological, biochemical and morphological indicators of normal and obese rats

Specialized products and dietary supplements, enriched with complexes of minor biologically active substances (BAS), are often offered as components of therapeutic diets in the treatment of obesity and metabolic syndrome. At the same time, the possible effects of the interactions of BAS when consuming a multicomponent product have not been studied enough. The aim - to study the action on rats' organism of a complex supplement (RС), containing resveratrol (Res) and L-carnitine (L-Car), when consumed with a standard balanced or hypercaloric diet. Material and methods. Male Wistar rats received for 63 days a standard balanced diet (SD) or a high-fat-high-carbohydrate diet (HFCD) with an excess of total fat (30%) and fructose (20% solution instead of drinking water), or the same diets supplemented with RС in a low (25 mg/kg body weight as Res and 300 mg/kg body weight as L-Car) or high (50 and 600 mg/kg body weight, respectively) doses. The muscle grip strength, behavioral reactions in tests of the conditioned passive avoidance reflex (CPAR) and elevated plus maze (EPM) were studied. At the end of the experiment, the mass of adipose tissue and internal organs was determined together with the activity of microsomal and cytosolic liver enzymes for specific substrates, plasma biochemical parameters, liver morphology by lightoptical microscopy, accumulation of lipofuscin-like granules (LLG) in the liver and kidneys by laser confocal microscopy. Results. In the rats fed HFCD, compared with SD, there was an increase in the mass index of liver, total inguinal and retroperitoneal white adipose tissue, in the levels of glucose and triglycerides, in the activity of hepatic CYP1A1 and CYP3A monooxygenases, UDPglucuronosyltransferase, heme oxygenase, and simultaneous decrease of high and low density lipoprotein cholesterol, and quinone oxidoreductase activity. The RС intake stimulated the locomotor activity of rats in EPM, however, this effect was less pronounced against the background of HFCD consumption. In rats consuming SD (but not HFCD), the addition of RС caused an increase in search activity and anxiety according to the EPM and CPAR data. The effect on short- and long-term memory retention was statistically insignificant. RС intake did not have hypolipidemic and hypoglycemic properties but caused in low dose an increase in the ratio of the activity of transaminases AST/ALT in animals fed HFCD. The liver CYP3A activity increased in rats supplemented with RС in high dose fed HFCD. In the kidneys of animals, the consumption of RС resulted in increased accumulation of LLG. Conclusion. When studying the effect of the complex supplement RС on normal and obese rats according to the studied physiological, morphological and biochemical indexes, no positive effects were revealed, that would not have manifested themselves for Res and L-Car separate intake. No evidence of synergistic action of L-Car and Res were found, and some of the effects of the complex supplement can be considered as adverse. This requires careful assessment when combined using these substances in complex diet therapy of metabolic disorders in humans.