The Baseline Serum Lipoprotein Profile Is Related to Plant Stanol Induced Changes in Serum Lipoprotein Cholesterol and Triacylglycerol Concentrations

Objective: Baseline characteristics of subjects might be related to the effect of plant stanols on the serum lipoprotein profile. The aim of the study was to examine effects of subjects’ baseline characteristics (baseline serum concentrations of lipids and lipoproteins at the start of the study, lathosterol, campesterol and sitosterol; gender, age, BMI, smoking, use of oral contraceptives and menopause) on the effects of plant stanol esters on the serum lipoprotein profile.

Methods: We used data of five studies performed at our Department. A random intercept model was used for statistical analysis, using serum lipid and lipoprotein concentrations after plant stanol ester consumption, as dependent variables.

Results: After plant stanol ester consumption, higher baseline serum concentrations of total and LDL cholesterol resulted in larger absolute decreases in their respective serum concentrations. For the ratio of total to HDL cholesterol and triacylglycerol, higher baseline serum levels resulted in larger absolute and relative decreases in their serum levels. HDL cholesterol concentrations increased in subjects with low baseline concentrations and decreased in those with high baseline concentrations. Effects however were small. No relationships were observed with baseline serum cholesterol-standardized lathosterol and campesterol concentrations, although LDL cholesterol concentrations tended to decrease more at higher baseline sitosterol concentrations. No effects of other baseline characteristics were found.

Conclusions: People with an unfavorable serum lipid and lipoprotein profile benefit even more of plant stanols than people with a more favorable profile.     

Assessment of Plant Sterols in the Diet of Adult Polish Population with the Use of a Newly Developed Database

Plant sterols are compounds with multiple biological functions, mainly cholesterol-reducing. There are no comprehensive databases on plant sterols, which makes it difficult to estimate their intake in the Polish population. This work attempted to use international food databases, additionally supplemented by scientific data from the literature, to create a database of plant sterols, which would cover various kinds of foods and dishes consumed in Poland. The aim was to assess the size and sources of dietary plant sterols in the adult population of Poland. The literature search was conducted using PubMed, Web of Science, Scopus, and Google Scholar to identify possible sources of published food composition data for plant sterols. The study group consisted of 5690 participants of the WOBASZ II survey. We identified 361 dietary sources of plant sterols based on the consumption of foods and dishes reported by participants. Cereals and fats provided 61% of the total plant sterols, and together with vegetables and fruits, this totaled 80%. The median intake of plant sterols in the Polish population was 255.96 mg/day, and for men and women 291.76 and 230.61 mg/day, respectively. Canola oil provided the most plant sterols at 16.92%, followed by white bread at 16.65% and soft margarine at 8.33%. The study found that plant sterol intake in Poland is comparable to other populations, and women’s diets are more dense in plant sterols. Due to the lack of literature sources on plant sterol content in some foods, future studies should expand and complete the databases on plant sterol content in foods.     

Cholesterol-Lowering Efficacy of Plant Sterols in Low-Fat Yogurt Consumed as a Snack or with a Meal

Objective: Plant sterols (PS) consumed as a snack may not have the same cholesterol-lowering potential as when consumed with a meal due to poor solubilization. It was hypothesized that the consumption of a single dose, low-fat yogurt rich in PS (1.6 g/d) with a meal over an afternoon snack will lead to favourable changes in plasma lipids, plasma PS concentrations, and cholesterol synthesis without negatively affecting α-tocopherol or carotenoids levels.

Methods: Twenty-six hyperlipidemic males and females completed the randomized trial of three phases (control, single PS dose consumed with a meal, or single PS dose as an afternoon snack) while consuming controlled, low-fat diets. Plasma lipids, cholesterol synthesis rates, plasma PS and serum fat-soluble antioxidants were measured at baseline and after 4 weeks.

Results: Endpoint total cholesterol (TC) levels after the PS snack phase were decreased (p = 0.04) (5.30 ± 0.2 mmol/L) compared to the control phase (5.53 ± 0.2 mmol/L). However, endpoints for TC (5.37 ± 0.2 mmol/L) for PS dose with a meal were comparable to control phase. Low-density lipoprotein-cholesterol tended to be different (p = 0.06) at the end of the intervention phases (3.51 ± 0.1, 3.43 ± 0.1, and 3.33 ± 0.1 mmol/L; control, meal and snack, respectively). Cholesterol fractional synthesis rates were higher (p = 0.007) by 25.8% and 19.5% at the end of the snack and meal phases, respectively, compared with the control phase. Plasma campesterol and β-sitosterol concentrations, adjusted for TC, were higher (p < 0.01) in the snack phase (2.30 ± 0.3 and 0.54 ± 0.1 μmol/mmol, respectively) and in the meal phase (2.00 ± 0.3 and 0.51 ± 0.1 μmol/mmol, respectively) when compared to the control phase (1.81 ± 0.3 and 0.40 ± 0.1 μmol/mmol, respectively). No changes in α-tocopherol or carotenoids levels were detected after adjusting for TC, for all phases.

Conclusion: These results indicate that a single dose of PS in low-fat yogurt, provided as a snack, lowers cholesterol levels but does not alter fat-soluble vitamin or carotenoid concentrations in hyperlipidemic participants.     

调节性T细胞在大鼠TNBS诱发实验性结肠炎中作用的研究

目的　探讨CD4+ CD2 5+ 和CD8+ CD2 8-调节性T细胞在TNBS(2 ,4,6-三硝基苯磺酸 )诱发的大鼠实验性结肠炎的外周血、脾脏、结肠的改变及其作用。方法　建立TNBS实验性结肠炎大鼠模型 ,设对照组、建模后第一周和第三周三组 ,用流式细胞仪检测各组外周血、脾脏和结肠黏膜上皮细胞内单个核细胞中CD4+ CD2 5+ 和CD8+ CD2 8-调节性T细胞比例的变化。结果　成功建立TNBS大鼠实验性结肠炎模型 (n =15 )。结肠部位CD8+ CD2 8-细胞在建模后第一周时较对照组均明显增高 [(12 7± 5 4) %vs(3 87± 3 7) % ,P <0 0 1]。在外周血、脾和结肠中CD8+ CD2 8-T细胞比例在建模第三周时均较对照组明显增加 [外周血 :(14 4± 5 5 ) %vs(6 5± 4 6) % ,脾脏 :(18 7± 4 9) %vs(7 2± 5 7) % ,结肠 :(16 3± 4 9) %vs(3 87± 3 7) % ,P <0 0 1] ,其中以结肠部位增加最高 ,同其它两部位比较有统计学差异 (2 8± 0 6vs 1 1± 0 4,2 8± 0 6vs 1 5± 0 4,P <0 0 5 )。在第一周 ,CD4+ CD2 5+ T细胞在结肠部位较对照组增加 [(13 6± 6 1)vs(5 7± 4 2 ) ,P <0 0 5 ] ,于第三周回落至对照组水平。结论　CD4+ CD2 5+ 和CD8+ CD2 8-T细胞在TNBS实验性结肠炎大鼠模型中较正常对照组有明显增加 ,但增加的部位和时间点     

Protective Effects of Dietary Resveratrol against Chronic Low-Grade Inflammation Mediated through the Gut Microbiota in High-Fat Diet Mice

Resveratrol (RSV), a natural polyphenol, has been shown to exert activity against obesity and related chronic inflammation. However, due to the poor bioavailability of RSV, the mechanisms of RSV against inflammation in obesity models remain unclear. In this study, we aimed to investigate the relationship between the gut bacteria and the anti-inflammation effects of RSV in HFD-fed mice. We found that RSV supplementation reduced fat accumulation and improved systemic inflammation in HFD-fed mice. Meanwhile, RSV attenuated HFD-induced changes in the gut microbiota’s structure, which were associated with inflammatory parameters. A fecal microbiota transplantation (FMT) experiment proved that the anti-inflammation effects of RSV largely rely on the gut microbiota. Moreover, the microbiota-genera-changing trend in the FMT experiment was similar to that in the oral RSV-feeding experiment. Thus, these results demonstrate that modulation of the gut bacteria induced by RSV treatment has a therapeutic effect on chronic low-grade inflammation in HFD-fed mice.     

Effects of Dietary Protein Intake on Cutaneous and Systemic Inflammation in Mice with Acute Experimental Psoriasis

Background: Psoriasis is a systemic inflammatory disorder, primarily characterized by skin plaques. It is linked to co-morbidities including cardiovascular disease and metabolic syndrome. Several studies demonstrate that dietary habits can influence psoriasis development and severity. However, the effect of different dietary protein levels on psoriasis development and severity is poorly understood. In this study, we examine the influence of dietary protein on psoriasis-like skin disease in mice. Methods: We fed male C57BL/6J mice with regular, low protein and high protein chow for 4 weeks. Afterwards, we induced psoriasis-like skin disease by topical imiquimod (IMQ)-treatment on ear and back skin. The local cutaneous and systemic inflammatory response was investigated using flow cytometry analysis, histology and quantitative rt-PCR. Results: After 5 days of IMQ-treatment, both diets reduced bodyweight in mice, whereas only the high protein diet slightly aggravated IMQ-induced skin inflammation. IMQ-treatment induced infiltration of myeloid cells, neutrophils, and monocytes/macrophages into skin and spleen independently of diet. After IMQ-treatment, circulating neutrophils and reactive oxygen species were increased in mice on low and high protein diets. Conclusion: Different dietary protein levels had no striking effect on IMQ-induced psoriasis but aggravated the systemic pro-inflammatory phenotype.     

Probiotic Bacillus Spores Together with Amino Acids and Immunoglobulins Exert Protective Effects on a Rat Model of Ulcerative Colitis

In inflammatory bowel disease (IBD), experimental models have proven to be important tools for evaluating potential therapeutic agents and for investigating the mechanisms of pathogenesis. Oxidative stress and the immune response have been associated with acetic acid (AA)-induced ulcerative colitis (UC). Our study aimed to evaluate, for the first time, the ability of a spore-based probiotic and an amino acid and immunoglobulin supplement in reducing tissue damage and inflammatory responses in an experimental animal model of UC. Forty-two Wistar rats were divided into six groups, receiving 1% carboxymethylcellulose, 4% AA, MegaSporeBiotic™ (MSB; 1 × 10⁹ colony forming units/day) and MegaMucosa™ (MM; 70 mg/100 g/day). Pretreatment with MSB or MM alone and in combination significantly lowered inflammation and reduced damage to the colonic mucosa. Pretreatment with these agents resulted in levels of proinflammatory cytokines, vascular tight junction proteins, and measures of oxidative stress similar to those reported for methylprednisolone, one of the first-line therapies for moderate to severe activity of UC. The protection was further confirmed by histologic analysis of the colon tissue. In conclusion, pretreatment with probiotic spore-forming Bacillus strains and a supplement of amino acids in combination with immunoglobulins exhibited anti-inflammatory and antioxidant effects in an AA-induced rat model of UC.     

Dyslipidaemia Is Associated with Severe Disease Activity and Poor Prognosis in Ulcerative Colitis: A Retrospective Cohort Study in China

Background: Clinical data on the correlation of dyslipidaemia with the long-term outcomes of ulcerative colitis (UC) are limited. This study aimed to evaluate the impact of lipid levels on disease activity and prognosis in UC. Methods: The retrospective data of UC patients who had detailed lipid profiles were collected from January 2003 to September 2020. All patients were followed-up to 30 September 2021. The long-term outcomes were UC-related surgery and tumorigenesis. Results: In total, 497 patients were included in the analysis. Compared to patients with normal lipid levels, those with dyslipidaemia commonly presented with more serious disease activity. Low high-density lipoprotein cholesterol (p < 0.05) levels were associated with higher risks of severe disease activity in UC. Regarding the long-term outcomes, patients with persistent dyslipidaemia were at higher risks of UC-related surgery (HR: 3.27, 95% CI: 1.86–5.75, p < 0.001) and tumorigenesis (HR: 7.92, 95% CI: 3.97–15.78, p < 0.001) and had shorter surgery- and tumour-free survival (p < 0.001) than patients with transient dyslipidaemia and normal lipid levels. Low levels of high-density lipoprotein cholesterol (p < 0.001) and apolipoprotein A1 (p < 0.05) were associated with higher risks of surgery and tumorigenesis. Conclusion: Persistent dyslipidaemia was associated with a higher risk of serious disease activity and worse long-term outcomes among patients with UC. Lipid patterns should be assessed to improve the management of high-risk patients with UC in the early phase.     

The Role of Dietary Supplementation with Plant Sterols and Stanols in the Prevention of Cardiovascular Disease

Several studies have shown that increased levels of low-density lipoprotein (LDL) cholesterol predict cardiovascular events. The Adult Treatment Panel II (ATP II) introduced the principle of therapeutic lifestyle changes, including plant sterols/stanols for the management of LDL cholesterol. Plant sterols and stanols in fat matrices effectively lower LDL cholesterol levels in hypercholesterolemic, diabetic, and healthy human volunteers. Recent studies also show that sterols (2 g/d) lower LDL cholesterol even when incorporated in nonfat matrices. In addition, they may reduce biomarkers of oxidative stress and inflammation. Plant sterols and stanols exert their hypocholes-terolemic effects possibly by interfering with the uptake of both dietary and biliary cholesterol from the intestinal tract. Present evidence is accumulating to promote their use for lowering LDL cholesterol levels, as a first line of therapy (as well as adjunctive therapy) in patients on statin therapy.     

Effects of yoghurt enriched with free plant sterols on the levels of serum lipids and plant sterols in moderately hypercholesterolaemic subjects on a high-fat diet

Apparently, one of the primary reasons for purchasing organic food is the perception that it is more nutritious than conventional food. Given the increasing interest towards organic food products, it is imperative to review the existing literature concerning the nutritional value of the produce, and to determine to what extent are consumer expectations met. There are only few well-controlled studies that are capable of making a valid comparison and, therefore, compilation of the results is difficult and generalisation of the conclusions should be made with caution. In spite of these limitations, however, some differences can be identified. Although there is little evidence that organic and conventional foods differ in respect to the concentrations of the various micronutrients (vitamins, minerals and trace elements), there seems to be a slight trend towards higher ascorbic acid content in organically grown leafy vegetables and potatoes. There is also a trend towards lower protein concentration but of higher quality in some organic vegetables and cereal crops. With respect to the rest of the nutrients and the other food groups, existing evidence is inadequate to allow for valid conclusions. Finally, animal feeding experiments indicate that animal health and reproductive performance are slightly improved when they are organically fed. A similar finding has not yet been identified in humans. Several important directions can be highlighted for future research; it seems, however, that despite any differences, a well-balanced diet can equally improve health regardless of its organic or conventional origin.     

Influence of Plant and Animal Proteins on Inflammation Markers among Adults with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

Proteins, especially plant proteins, may reduce inflammation among adults with chronic kidney disease (CKD). This systematic review and meta-analysis were conducted to evaluate the effect protein types (animal or plant) have on inflammation markers (CRP, IL-6, TNF-α) among adults with varying stages of CKD. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was conducted to identify articles from inception until January 2021, utilizing six databases. Controlled trials that compared the effects of different protein types were analyzed using random-effects meta-analysis. Quality assessment and risk of bias of the included articles were assessed by using Cochrane risk of bias instrument and ROBINS-I. Out of the 10 studies that met the criteria, there was a decreasing trend in CRP levels when consuming plant proteins compared to animal proteins among non-dialysis participants. There was a statistically significant decrease when comparing animal proteins to unspecified proteins in CRP levels among dialysis participants [Hedges’ g = 2.11; 95% CI 1.12, 3.11; p ≤ 0.001], favoring unspecified proteins. Furthermore, animal proteins (eggs, red meat) showed increasing trends in CRP levels compared to whey protein isolate. Caution must be considered regarding these results as controlled, non-randomized, trials were included in the analysis, which may have contributed to high risk of bias. Future research should focus on protein types and the impact they have on kidney disease progression and inflammation markers.     

Assessing the Physiological Effects of Traditional Regional Diets Targeting the Prevention of Cardiovascular Disease: A Systematic Review of Randomized Controlled Trials Implementing Mediterranean,New Nordic,Japanese, Atlantic,Persian and Mexican Dietary Interventions

Traditional regional diets are considered as sustainable dietary patterns, while many have been examined with regard to their health benefits. The aim of the present systematic review was to aggerate all evidence on the physiological effects of regional diets among adults at high risk for cardiovascular disease (CVD). Three databases were searched for randomized controlled trials (RCTs) implementing any regional diet (Mediterranean (MedD), Persian, Southern European Atlantic, Japanese, Chinese, new Nordic, or other) while examining cardiovascular risk factors among adults at increased risk. Primary outcomes included anthropometric indices and secondary outcomes involved blood lipid concentrations, glucose metabolism, inflammation and other markers of CVD progression. Twenty RCTs fulfilled the study’s criteria and were included in the qualitative synthesis, with the majority implementing a MedD. Adherence to most of the regional diets induced a reduction in the BW and anthropometric indices of the participants. The majority of RCTs with blood pressure endpoints failed to note a significant reduction in the intervention compared to the comparator arm, with the exception of some new Nordic and MedD ones. Despite the interventions, inflammation markers remained unchanged except for CRP, which was reduced in the intervention groups of one new Nordic, the older Japanese, and the Atlantic diet RCTs. With regard to blood lipids, regional diet interventions either failed to induce significant differences or improved selective blood lipid markers of the participants adhering to the experimental regional diet arms. Finally, in the majority of RCTs glucose metabolism failed to improve. The body of evidence examining the effect of regional dietary patterns on CVD risk among high-risk populations, while employing an RCT design, appears to be limited, with the exception of the MedD. More research is required to advocate for the efficacy of most regional diets with regard to CVD.     

Dietary Supplementation with Black Raspberries Altered the Gut Microbiome Composition in a Mouse Model of Colitis-Associated Colorectal Cancer,although with Differing Effects for a Healthy versus a Western Basal Diet

Black raspberries (BRB) are rich in anthocyanins with purported anti-inflammatory properties. However, it is not known whether dietary supplementation would ameliorate Western-diet enhanced gut inflammation and colon tumorigenesis. We employed a mouse model of colitis-associated colorectal cancer (CAC) to determine the effects of dietary supplementation with 5 to 10% (w/w) whole, freeze-dried BRB in male C57BL/6J mice fed either a standard healthy diet (AIN93G) or the total Western diet (TWD). In a pilot study, BRB suppressed colitis and colon tumorigenesis while also shifting the composition of the fecal microbiome in favor of taxa with purported health benefits, including Bifidobacterium pseudolongum. In a follow-up experiment using a 2 × 2 factorial design with AIN and TWD basal diets with and without 10% (w/w) BRB, supplementation with BRB reduced tumor multiplicity and increased colon length, irrespective of the basal diet, but it did not apparently affect colitis symptoms, colon inflammation or mucosal injury based on histopathological findings. However, BRB intake increased alpha diversity, altered beta diversity and changed the relative abundance of Erysipelotrichaceae, Bifidobacteriaceae, Streptococcaceae, Rikenellaceae, Ruminococcaceae and Akkermansiaceae, among others, of the fecal microbiome. Notably, changes in microbiome profiles were inconsistent with respect to the basal diet consumed. Overall, these studies provide equivocal evidence for in vivo anti-inflammatory effects of BRB on colitis and colon tumorigenesis; yet, BRB supplementation led to dynamic changes in the fecal microbiome composition over the course of disease development.     

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.     

Effects of Diet-Induced Weight Loss on Plasma Markers for Cholesterol Absorption and Synthesis: Secondary Analysis of a Randomized Trial in Abdominally Obese Men

Cross-sectional studies have shown that obesity is associated with lower intestinal cholesterol absorption and higher endogenous cholesterol synthesis. These metabolic characteristics have also been observed in patients with type 2 diabetes, metabolic syndrome, steatosis or cholestasis. The number of intervention studies evaluating the effect of weight loss on these metabolic characteristics is, however, limited, while the role of the different fat compartments has not been studied into detail. In a randomized trial, abdominally obese men (N = 54) followed a 6-week very low caloric (VLCD) diet, followed by a 2 week weight-maintenance period. Non-cholesterol sterols were measured at baseline and after 8 weeks, and compared to levels in lean participants (N = 25). After weight loss, total cholesterol (TC)-standardized cholestanol levels increased by 0.18 µmol/mmol (p < 0.001), while those of campesterol and lathosterol decreased by 0.25 µmol/mmol (p < 0.05) and 0.39 µmol/mmol (p < 0.001), respectively. Moreover, after weight loss, TC-standardized lathosterol and cholestanol levels were comparable to those of lean men. Increases in TC-standardized cholestanol after weight loss were significantly associated with changes in waist circumference (p < 0.01), weight (p < 0.001), BMI (p < 0.001) and visceral fat (p < 0.01), but not with subcutaneous and intrahepatic lipids. In addition, cross-sectional analysis showed that visceral fat fully mediated the association between BMI and TC-standardized cholestanol levels. Intrahepatic lipid content was a partial mediator for the association between BMI and TC-standardized lathosterol levels. In conclusion, diet-induced weight loss decreased cholesterol synthesis and increased cholesterol absorption. The increase in TC-standardized cholestanol levels was not only related to weight loss, but also to a decrease in visceral fat volume. Whether these metabolic changes ameliorate other metabolic risk factors needs further study.     

Dietary Management of Chronic Kidney Disease and Secondary Hyperoxaluria in Patients with Short Bowel Syndrome and Type 3 Intestinal Failure

Short gut syndrome can lead to type 3 intestinal failure, and nutrition and hydration can only be achieved with parenteral nutrition (PN). While this is a lifesaving intervention, it carries short- and long-term complications leading to complex comorbidities, including chronic kidney disease. Through a patient with devastating inflammatory bowel disease’s journey, this review article illustrates the effect of short gut and PN on kidney function, focusing on secondary hyperoxaluria and acute precipitants of glomerular filtration. In extensive small bowel resections colon in continuity promotes fluid reabsorption and hydration but predisposes to hyperoxaluria and stone disease through the impaired gut permeability and fat absorption. It is fundamental, therefore, for dietary intervention to maintain nutrition and prevent clinical deterioration (i.e., sarcopenia) but also to limit the progression of renal stone disease. Adaptation of both enteral and parenteral nutrition needs to be individualised, keeping in consideration not only patient comorbidities (short gut and jejunostomy, cirrhosis secondary to PN) but also patients’ wishes and lifestyle. A balanced multidisciplinary team (renal physician, gastroenterologist, dietician, clinical biochemist, pharmacist, etc.) plays a core role in managing complex patients, such as the one described in this review, to improve care and overall outcomes.     

Dietary Effects of Chromium Picolinate and Chromium Nanoparticles in Wistar Rats Fed with a High-Fat,Low-Fiber Diet: The Role of Fat Normalization

We aimed to evaluate how feeding a high-fat–low-fiber (F) diet to rats and dietary intervention with the implementation of a standard-fat-and-fiber (S) diet affects the response of the cardiovascular system to chromium (III) picolinate (Cr–Pic) and, alternatively, chromium nanoparticles (Cr–NPs). Young male Wistar Han rats (n/group = 12) from either the fatty group (18 weeks on F diet) or the intervention group (9 weeks on F diet + 9 weeks on S diet) received a pharmacologically relevant dose of 0.3 mg Cr/kg body weight in the form of Cr–Pic or Cr–NPs for 9 weeks. Our study on rats confirmed the pro-inflammatory effect of an F diet administered for 18 weeks. In the intervention group, both Cr–Pic and Cr–NPs decreased heart glutathione ratio (GSH+GSSG), enhanced participation of nitric oxide (NO) derived from inducible NO synthase (iNOS) in vascular relaxation to acetylcholine (ACh), increased the vasodilator net effect of cyclooxygenase-2 (COX-2)-derived prostanoids, and increased the production of superoxide anion (O₂^.−) in aortic rings. Meanwhile, in the fatty group, there was increased heart superoxide dismutase (SOD), decreased heart catalase (CAT), and reduced sensitivity in pre-incubated aortic rings to endogenous prostacyclin (PGI₂). The factors that significantly differentiated Cr–NPs from Cr–Pic were (i) decreased blood antioxidant capacity of water-soluble compounds (0.75-fold, p = 0.0205), (ii) increased hydrogen peroxide (H₂O₂) production (1.59-fold, p = 0.0332), and (iii) modified vasodilator response due to PGI₂ synthesis inhibition (in the intervention group) vs. modified ACh-induced vasodilator response due to (iv) COX inhibition and v) PGI₂ synthesis inhibition with thromboxane receptor blockage after 18 weeks on F diet (in the fatty group). Our results show that supplementation with Cr–Pic rather than with Cr–NPs is more beneficial in rats who regularly consumed an F diet (e.g., for 18 weeks). On the contrary, in the intervention group (9 weeks on F diet + 9 weeks of dietary fat normalization (the S diet)), Cr–Pic and Cr–NPs could function as pro-oxidant agents, initiating free-radical reactions that led to oxidative stress.     

Attenuation of Oxidative Stress and Inflammatory Response by Chronic Cannabidiol Administration Is Associated with Improved n-6/n-3 PUFA Ratio in the White and Red Skeletal Muscle in a Rat Model of High-Fat Diet-Induced Obesity

The consumption of fatty acids has increased drastically, exceeding the nutritional requirements of an individual and leading to numerous metabolic disorders. Recent data indicate a growing interest in using cannabidiol (CBD) as an agent with beneficial effects in the treatment of obesity. Therefore, our aim was to investigate the influence of chronic CBD administration on the n-6/n-3 polyunsaturated fatty acids (PUFAs) ratio in different lipid fractions, inflammatory pathway and oxidative stress parameters in the white and red gastrocnemius muscle. All the designed experiments were performed on Wistar rats fed a high-fat diet (HFD) or a standard rodent diet for seven weeks and subsequently injected with CBD (10 mg/kg once daily for two weeks) or its vehicle. Lipid content and oxidative stress parameters were assessed using gas–liquid chromatography (GLC), colorimetric and/or immunoenzymatic methods, respectively. The total expression of proteins of an inflammatory pathway was measured by Western blotting. Our results revealed that fatty acids (FAs) oversupply is associated with an increasing oxidative stress and inflammatory response, which results in an excessive accumulation of FAs, especially of n-6 PUFAs, in skeletal muscles. We showed that CBD significantly improved the n-6/n-3 PUFA ratio and shifted the equilibrium towards anti-inflammatory n-3 PUFAs, particularly in the red gastrocnemius muscle. Additionally, CBD prevented generation of lipid peroxidation products and attenuated inflammatory response in both types of skeletal muscle. In summary, the results mentioned above indicate that CBD presents potential therapeutic properties with respect to the treatment of obesity and related disturbances.