Glycyrrhizic Acid Can Attenuate Metabolic Deviations Caused by a High-Sucrose Diet without Causing Water Retention in Male Sprague-Dawley Rats

Glycyrrhizic acid (GA) ameliorates many components of the metabolic syndrome, but its potential therapeutic use is marred by edema caused by inhibition of renal 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2). We assessed whether 100 mg/kg per day GA administered orally could promote metabolic benefits without causing edema in rats fed on a high-sucrose diet. Groups of eight male rats were fed on one of three diets for 28 days: normal diet, a high-sucrose diet, or a high-sucrose diet supplemented with GA. Rats were then culled and renal 11β-HSD2 activity, as well as serum sodium, potassium, angiotensin II and leptin levels were determined. Histological analyses were performed to assess changes in adipocyte size in visceral and subcutaneous depots, as well as hepatic and renal tissue morphology. This dosing paradigm of GA attenuated the increases in serum leptin levels and visceral, but not subcutaneous adipocyte size caused by the high-sucrose diet. Although GA decreased renal 11β-HSD2 activity, it did not affect serum electrolyte or angiotensin II levels, indicating no onset of edema. Furthermore, there were no apparent morphological changes in the liver or kidney, indicating no toxicity. In conclusion, it is possible to reap metabolic benefits of GA without edema using the current dosage and treatment time

N-Acetylcysteine an Allium Plant Compound Improves High-Sucrose Diet-Induced Obesity and Related Effects

This study was designed to determine whether N-acetylcysteine (NAC, C5H9–NO3S), a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6) and those receiving high-sucrose diet (HS, n = 18). After 22 days, (HS) group was divided into three groups (n = 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l−1-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l­1-NAC in its drinking water. After 22 days of the HS-group division (44 days of experimental period) body weight, body mass index and surface area were enhanced in HS-HS rats (P < .001). HS-HS rats had glucose intolerance, increased serum triacylglycerol (TG), very low-density lipoprotein (VLDL), oxidized-LDL (ox-LDL) and lipid-hydroperoxide (LH) than the others (P < .01). NAC in HS-N and HS-CN rats reduced the obesity markers, feed efficiency, LH and ox-LDL, as well normalized glucose response, TG and VLDL (P < .01) in these groups compared with HS-HS. Total antioxidant substances, GSH/GSSG ratio and glutathione-reductase, were higher in HS-N than in HS-HS (P < .01). In conclusion, NAC improved high-sucrose diet-induced obesity and its effects on glucose tolerance, lipid profile, in vivo LDL-oxidation and serum oxidative stress, enhancing antioxidant defences. The application of this agent may be feasible and beneficial for high-sucrose diet-induced obesity, which certainly would bring new insights on obesity-related adverse effects control

A Lipoprotein Lipase–Promoting Agent, NO-1886, Improves Glucose and Lipid Metabolism in High Fat, High Sucrose–Fed New Zealand White Rabbits

The synthetic compound NO-1886 is a lipoprotein lipase activator that lowers plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C). Recently, the authors found that NO-1886 also had an action of reducing plasma glucose in high-fat/high-sucrose diet–induced diabetic rabbits. In the current study, we investigated the effects of NO-1886 on insulin resistance and β-cell function in rabbits. Our results showed that high-fat/high-sucrose feeding increased plasma triglyceride, free fatty acid (FFA), and glucose levels and decreased HDL-C level. This diet also induced insulin resistance and impairment of acute insulin response to glucose loading. Supplementing 1% NO-1886 into the high-fat/high-sucrose diet resulted in decreased plasma triglyceride, FFA, and glucose levels and increased HDL-C level. The authors also found a clear increased glucose clearance and a protected acute insulin response to intravenous glucose loading by NO-1886 supplementation. These data suggest that NO-1886 suppresses the elevation of blood glucose in rabbits induced by feeding a high-fat/high-sucrose diet, probably through controlling lipid metabolism and improving insulin resistance

Dynamic shifts in the composition of resident and recruited macrophages influence tissue remodeling in NASH

Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM

Effects of a high-sucrose diet and systemic inflammation on Alzheimer’s disease-related processes in reproductively normal female wild-type mice

Alzheimer’s disease (AD) incidence is expected to double by 2038. This coincides with similar trends in obesity and chronic inflammation. It is known that insulin resistant and chronic inflammatory conditions can increase the risk of AD-like neurodegeneration, likely through mechanisms involving induction of brain insulin resistance. Insulin resistant brain states are associated with increased activity of glycogen synthase kinase-3β (GSK-3β), whose constitutive activity is inhibited, in part, by activity within the insulin pathway. Aberrant GSK-3β signaling contributes to increased amyloid-β production (senile plaques) and Tau protein hyperphosphorylation (neurofibrillary tangles), hallmarks of AD-like neurodegeneration. In addition, nearly two-thirds of AD patients are female, which strongly suggests a role for the post-menopausal loss of the female sex hormone, estrogen, in the pathogenic events associated with AD. Estrogen is known to diminish neurodegenerative processes, such as β-amyloidopathy, mitochondrial dysfunction and oxidative stress, in a variety of animal models. A reduction in estrogen levels following menopause has also been associated with increased risk of insulin resistance and inflammation, thus necessitating exploration of the neurodegenerative potential of these conditions in a female animal model. As a first step, by combining a high-sucrose diet (20% of the drinking water) with intraperitoneal LPS injections (0.1 mg/kg; once/month for 3 months) over seven months in reproductively normal female wild-type mice (C57Bl/6; n=10/group), a protective effect of low-dose LPS on high-sucrose diet-induced pathology was demonstrated. Results from the high-sucrose group confirmed that a high-sucrose diet is a suitable model of neurodegeneration, as evidenced by exaggerated glucocorticoid expression, spatial learning deficits, irregularities within the insulin pathway, and increased β-amyloid production and Tau phosphorylation. Interestingly, while LPS had little to no effect in isolation, it exerted a protective influence when added to animals sustained on a high-sucrose diet. Corticosterone homeostasis, Aβ and pTau levels, and insulin pathway second messenger expression were all rescued following addition of LPS. Given the hypothesized role of increased GSK-3β activity in neurodegeneration, mice following the combined treatment regimen were supplemented with lithium orotate (1 mg/L in the drinking water), a potent inhibitor of GSK-3β, to assess its prophylactic potential against dietary- and-inflammatory insult-mediated neurodegeneration. As the addition of LPS to animals on a high-sucrose diet proved to be protective rather than aggravating, I was unable to assess lithium for prophylaxis against neurodegeneration. However, antagonistic interactions between LPS and lithium were observed (lithium blocked the effects of LPS). When added to mice following the combined regimen, lithium returned corticosterone and Aβ levels to those observed in animals sustained on high-sucrose alone, while completely abolishing spatial learning deficits and anxiety-like behavior. To sum, the work presented confirms a 1) high-sucrose diet as a model of neurodegeneration, 2) supports a protective role for transient inflammation against dietary-insult, and 3) suggests an antagonistic interaction between lithium and LPS

Effects of high sucrose diet, gemfibrozil, and their combination on plasma paraoxonase 1 activity and lipid levels in rats

We investigated the influence of high sucrose diet (HSD) after 3 or 5 weeks of administration on paraoxonase 1 (PON1) activity in plasma of normolipidemic rats and the relationship between serum PON1 activity, triacylglycerides (TGs), HDL and total cholesterol vs. the control group of rats fed normal, control diet (CD). Because the data about the influence of gemfibrozil (GEM) on PON1 activity are controversial, we also investigated its effects (administration in the 4th and 5th week in rats on HSD and CD) on plasma PON1 activity and lipid levels in normolipidemic rats, and in rats with hypertriglyceridemia caused by HSD. Our results obtained in rats on HSD show a significant increase of plasma TGs levels by 47% (P<0.05) after 5 weeks of treatment, and PON1 activity by 32% and 23% (P<0.05) after 3 and 5 weeks, but without change in lipid levels vs. rats on CD. In the rats on CD and HSD, GEM caused a significant decrease of PON1 activity by 44% and 33%, while a significant decrease of TGs level by 38% (P<0.05) was measured only in rats on CD. The effects of GEM on total cholesterol, HDL and LDL in both groups of rats were typical for its action on lipoprotein metabolism. Because GEM in the rat liver stimulates proliferation of peroxisomes, β oxidation, and production of H2O2, it is possible that the oxidative stress induced by GEM damages hepatocytes and lowers the synthesis of PON1

Elimination of high-refined-sugar diet as treatment strategy for autistic features induced in a rodent model

Purpose: To investigate the potency of ampicillin in altering gut flora in the presence of a high-sucrose diet in rat pups, and to determine its effect on selected neurotransmitters and a cytokine as markers of the persistent autistic features repeatedly induced in orally administered propionic acid rat pups..Methods: Twenty-eight young male Wistar albino rats were divided into four equal groups. The first group served as a control. The second group received an oral neurotoxic dose of propionic acid (PPA, 250 mg/kg body weight/day) for 3 days. The third group was treated with ampicillin (50 mg/kg for 3 weeks) with a standard diet. The fourth group was given the same dose of ampicillin with a high-sucrose diet for 10 weeks.Results: The results showed a significant (p &lt; 0.001) decrease in the investigated neurotransmitters in PPA- and ampicillin-treated rat pups (norepinephrine by 32.49 and 14.58 %, dopamine by 31.45 and 20.22 %, serotonin by 35.99 and 29.09 %), as well as a remarkable increase (p &lt; 0.001) in the proinflammatory cytokine, IL-6 (30.07and 6.07 %). The high-sucrose diet also significantly (p &lt; 0.001) enhanced the neurotoxic effect of ampicillin.Conclusion: The observed dietary modulation of the gut microbiota, coupled with the subsequent modulation of brain neurochemistry and inflammation, demonstrates the considerable potential of dietary intervention through the elimination of highly refined sugar as a treatment strategy to prevent and treat autism.Keywords: Neurotoxicity, Ampicillin, Propionic acid, Neurotransmitters, Cytokines, High-sucrose die

Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Triacylglycerol accumulation in the liver is a hallmark of NAFLD. Metabolic studies have confirmed that increased hepatic de novo lipogenesis (DNL) in humans contributes to fat accumulation in the liver and to NAFLD progression. Mice deficient in carboxylesterase (Ces)1d expression are protected from high-fat diet-induced hepatic steatosis. To investigate whether loss of Ces1d can also mitigate steatosis induced by over-activated DNL, WT and Ces1d-deficient mice were fed a lipogenic high-sucrose diet (HSD). We found that Ces1d-deficient mice were protected from HSD-induced hepatic lipid accumulation. Mechanistically, Ces1d deficiency leads to activation of AMP-activated protein kinase and inhibitory phosphorylation of acetyl-CoA carboxylase. Together with our previous demonstration that Ces1d deficiency attenuated high-fat diet-induced steatosis, this study suggests that inhibition of CES1 (the human ortholog of Ces1d) might represent a novel pharmacological target for prevention and treatment of NAFLD.Fil: Lian, Jihong. University of Alberta; CanadáFil: Watts, Russell. University of Alberta; CanadáFil: Quiroga, Ariel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; ArgentinaFil: Beggs, Megan R.. University of Alberta; CanadáFil: Alexander, R. Todd. University of Alberta; CanadáFil: Lehner, Richard. University of Alberta; Canad

High-fat but not sucrose intake is essential for induction of dyslipidemia and non-alcoholic steatohepatitis in guinea pigs

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and dyslipidemia are closely related. Diet plays an important role in the progression of these diseases, but the role of specific dietary components is not completely understood. Therefore, we investigated the role of dietary sucrose and fat/cholesterol on the development of dyslipidemia and NAFLD. METHODS: Seventy female guinea pigs were block-randomized (based on weight) into five groups and fed a normal chow diet (control: 4 % fat), a very high-sucrose diet (vHS: 4 % fat, 25 % sucrose), a high-fat diet (HF: 20 % fat, 0.35 % cholesterol), a high-fat/high-sucrose diet (HFHS: 20 % fat, 15 % sucrose, 0.35 % cholesterol) or a high-fat/very high-sucrose diet (HFvHS: 20 % fat, 25 % sucrose, 0.35 % cholesterol) for 16 and 25 weeks. RESULTS: All three high-fat diets induced dyslipidemia with increased concentrations of plasma cholesterol (p < 0.0001), LDL-C (p < 0.0001) and VLDL-C (p < 0.05) compared to control and vHS. Contrary to this, plasma triglycerides were increased in control and vHS compared to high-fat fed animals (p < 0.01), while circulating levels of free fatty acids were even between groups. Histological evaluation of liver sections revealed non-alcoholic steatohepatitis (NASH) with progressive inflammation and bridging fibrosis in high-fat fed animals. Accordingly, hepatic triglycerides (p < 0.05) and cholesterol (p < 0.0001) was increased alongside elevated levels of alanine and aspartate aminotransferase (p < 0.01) compared to control and vHS. CONCLUSION: Collectively, our results suggest that intake of fat and cholesterol, but not sucrose, are the main factors driving the development and progression of dyslipidemia and NAFLD/NASH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12986-016-0110-1) contains supplementary material, which is available to authorized users