Nicotinamide riboside supplementation exerts an anti-obesity effect and prevents inflammation and fibrosis in white adipose tissue of female diet-induced obesity mice.

Nicotinamide riboside (NR) is a nicotinamide adenine dinucleotide (NAD+) precursor. We previously reported that NR supplementation prevented the development of liver fibrosis in male mice. However, whether NR exerts a similar effect in females is unknown. Therefore, we determined whether NR supplementation can prevent obesity-induced inflammation and fibrosis in the liver and white adipose tissue (WAT) by providing NAD+ in obese female mice. Female C57BL/6J mice at the age of 8 weeks (young) and 16 weeks (old) were fed a high-fat/high-sucrose/high-cholesterol diet (HF) or HF diet supplemented with NR at 400 mg/kg/d for 20 weeks. While NR had minor effects in young female mice, it significantly reduced body weight gain, fat mass, glucose intolerance, and serum cholesterol levels compared to the HF group in old females. Hepatic NAD+ level tended toward an increase in the NR group (P=.054), but NR did not attenuate serum alanine aminotransferase levels, steatosis, and liver fibrosis in old female mice. However, NR decreased weight and adipocyte size in gonadal WAT (gWAT) of old females. NR also reduced the number of crown-like structures and the expression of inflammatory genes, along with decreases in fibrogenic gene expression and collagen accumulation in gWAT compared with the HF group. Also, old mice fed NR showed increased metabolic rates, physical activity, and energy expenditure compared with the HF. Thus, our results indicated that NR supplementation exerted an anti-obesity effect and prevented the development of inflammation and fibrosis in the WAT of old, but not young, female mice with diet-induced obesity.

Consumption of Low Dose Fucoxanthin Does Not Prevent Hepatic and Adipose Inflammation and Fibrosis in Mouse Models of Diet-Induced Obesity.

Fucoxanthin (FCX) is a xanthophyll carotenoid present in brown seaweed. The goal of this study was to examine whether FCX supplementation could attenuate obesity-associated metabolic abnormalities, fibrosis, and inflammation in two diet-induced obesity (DIO) mouse models. C57BL/6J mice were fed either a high-fat/high-sucrose/high-cholesterol (HFC) diet or a high-fat/high-sucrose (HFS) diet. The former induces more severe liver injury than the latter model. In the first study, male C57BL/6J mice were fed an HFC diet, or an HFC diet containing 0.015% or 0.03% (w/w) FCX powder for 12 weeks to develop obesity-induced nonalcoholic steatohepatitis (NASH). In the second study, mice were fed an HFS diet or an HFS diet containing 0.01% FCX powder for 8 weeks. FCX did not change body weight gain and serum lipid profiles compared to the HFC or HFS controls. No significant differences were present in liver triglyceride and total cholesterol, hepatic fat accumulation, and serum alanine aminotransferase levels between control and FCX-fed mice regardless of whether they were on an HFC or HFS diet. FCX did not mitigate mRNA abundance of genes involved in lipid synthesis, cholesterol metabolism, inflammation, and fibrosis in the liver and white adipose tissue, while hepatic fatty acid ß-oxidation genes were significantly elevated by FCX in both HFC and HFS feeding studies. Additionally, in the soleus muscle, FCX supplementation significantly elevated genes that regulate mitochondrial biogenesis and fatty acid ß-oxidation, concomitantly increasing mitochondrial DNA copy number, compared with HFC. In summary, FCX supplementation had minor effects on hepatic and white adipose inflammation and fibrosis in two different DIO mouse models.

Effects of Lavender on Anxiety, Depression, and Physiological Parameters: Systematic Review and Meta-Analysis.

PURPOSE: The recent evidence suggested substantial anxiolytic efficacy of lavender. The aim of this study was to examine the efficacy of lavender for anxiety, depression, and physiological parameters and to elucidate the differential effects of lavender on anxiety and depression by study characteristics. METHODS: A systematic review and meta-analysis was performed following the PRISMA guidelines. We searched PubMed, Embase, Cochrane Library, Web of Science, and Cumulative Index of Nursing and Allied Health Literature databases for randomized controlled trials investigating the efficacy of lavender on anxiety, depression, or physiological parameters in humans. We assessed the risk of bias within studies with the revised Cochrane risk of bias tool for randomized trials. We used random effect model to estimate the average effect and computed bias-corrected standardized mean difference as effect size metric, Hedges' g for all outcomes. RESULTS: Lavender was superior to placebo or no treatment in reducing anxiety (Hedges' g = -0.72, 95% confidence interval [CI] -0.90 to -0.55, p value <.001), depression (Hedges' g = -0.43, 95% CI, -0.59 to -0.27, p value <.001), and systolic blood pressure (Hedges' g = -0.23, 95% CI, -0.41to -0.05, p value = .01). The moderator analysis by meta-regression indicated that route of administration accounted 6.5% (p value = .187) for the heterogeneity in anxiolytic effects, sessions of treatment accounted 13.2% (p value = .055), and participants' health state accounted 8.9% (p value = .131) for the variance in anxiolytic effects. CONCLUSION: Lavender aromatherapy showed substantial effect in reducing anxiety and depression, and sessions of administration increased the anxiolytic effects. The effects on physiological parameters showed small with inconsistent significances and randomized controlled trials on the effect of lavender on depression were scarce. Future trials on depression and physiological parameters are recommended, and increasing the sessions of administration is recommended.

Anthocyanin-Rich Aronia Berry Extract Mitigates High-Fat and High-Sucrose Diet-Induced Adipose Tissue Inflammation by Inhibiting Nuclear Factor-κB Activation.

Obesity-induced inflammation in adipose tissue (AT) promotes the development of metabolic dysregulations by increasing macrophage recruitment in the stromal vascular fraction (SVF). The activation of nuclear factor-κB (NF-κB) signaling in macrophages serves as a pivotal mediator of AT inflammatory responses by increasing the expression of proinflammatory genes in obesity. Given the purported anti-inflammatory effects of berry consumption in humans, we evaluated if anthocyanin-rich aronia berry extract (ARN) can prevent obesity-induced AT inflammation in vivo. We also examined whether ARN suppresses lipopolysaccharide (LPS)-induced NF-κB activation in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). Male C57BL/6J mice were fed a low-fat diet, a high-fat (HF), and high-sucrose (HS) diet or HF/HS diet supplemented with 0.2% ARN (HF/HS + ARN) for 14 weeks. Compared to HF-/HS-fed mice, ARN supplementation tended to decrease fasting serum glucose (P = .07). Furthermore, ARN supplementation significantly inhibited the phosphorylation of NF-κB p65 in epididymal AT with a concomitant decrease in the expression of Cd11b and Tnfα mRNAs in epididymal SVF isolated, compared with those from HF-/HS-fed mice. Consistent with these in vivo findings, ARN treatment significantly decreased the phosphorylation of p65 in LPS-stimulated RAW 264.7 macrophages and BMDMs. Moreover, ARN suppressed LPS-induced mRNA expression of inflammation mediators (iNos, Cox-2, Tnfα, Mcp-1, and Il-6) and glycolysis markers (Glut1, G6pdh, and Hk1) in both cell types. Taken together, our in vivo and in vitro results suggest that ARN supplementation may attenuate obesity-induced AT inflammation by inhibiting NF-κB signaling and glycolytic pathway in macrophages.

How Strong is the Evidence for the Anxiolytic Efficacy of Lavender?: Systematic Review and Meta-analysis of Randomized Controlled Trials.

PURPOSE: Although lavender is purported to possess anxiolytic and sedative properties and is often recommended for relieving anxiety, the efficacy of lavender has not been well established. Thus, this review aimed to evaluate the anxiolytic effects of lavender aromatherapy. METHODS: Ten data bases were searched for studies published between 2000 and 2018. Randomized controlled trials investigating the anxiolytic effects of lavender aromatherapy with any type of application for persons with or without clinical anxiety were included. The outcome variables included self-rated anxiety, vital signs, and salivary cortisol and chromogranin A (CgA) levels. In the meta-analysis, standardized mean difference and 95% confidence interval were calculated as effect measures by applying the random effect model and inverse variance method. RESULTS: Twenty-two trials met our inclusion criteria. Lavender aromatherapy was found to have favorable effects in relieving anxiety (Hedges' g = -0.65; 95% CI, -0.84 to -0.46) and decreasing systolic blood pressure (g = -0.22; 95% CI, -0.43 to -0.02), heart rate (g = -0.53; 95% CI, -0.74 to -0.32), and salivary cortisol (g = -1.29; 95% CI, -2.23 to -0.35) and CgA (g = -2.29; 95% CI, -3.24 to -1.34) levels. However, the meta-analysis did not reveal any significant effects of lavender on diastolic blood pressure (effect size: -0.17; 95% CI, -0.37-0.04). CONCLUSION: Aromatherapy using lavender oil might have favorable effects on anxiety and its physiological manifestations. Future studies are recommended with an emphasis on methodological quality. In nursing practice, it is suggested that lavender aromatherapy be included in programs intended to manage anxiety in patients across diverse healthcare settings.

Nicotinamide riboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis.

OBJECTIVE: Liver fibrosis is part of the non-alcoholic fatty liver disease (NAFLD) spectrum, which currently has no approved pharmacological treatment. In this study, we investigated whether supplementation of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor, can reduce the development of liver fibrosis in a diet-induced mouse model of liver fibrosis. METHODS: Male C57BL/6 J mice were fed a low-fat control (LF), a high-fat/high-sucrose/high-cholesterol control (HF) or a HF diet supplemented with NR at 400 mg/kg/day (HF-NR) for 20 weeks. Features of liver fibrosis were assessed by histological and biochemical analyses. Whole-body energy metabolism was also assessed using indirect calorimetry. Primary mouse and human hepatic stellate cells were used to determine the anti-fibrogenic effects of NR in vitro. RESULTS: NR supplementation significantly reduced body weight of mice only 7 weeks after mice were on the supplementation, but did not attenuate serum alanine aminotransferase levels, liver steatosis, or liver inflammation. However, NR markedly reduced collagen accumulation in the liver. RNA-Seq analysis suggested that the expression of genes involved in NAD+ metabolism is altered in activated hepatic stellate cells (HSCs) compared to quiescent HSCs. NR inhibited the activation of HSCs in primary mouse and human HSCs. Indirect calorimetry showed that NR increased energy expenditure, likely by upregulation of ß-oxidation in skeletal muscle and brown adipose tissue. CONCLUSION: NR attenuated HSC activation, leading to reduced liver fibrosis in a diet-induced mouse model of liver fibrosis. The data suggest that NR may be developed as a potential preventative for human liver fibrosis.

Spirulina supplementation in a mouse model of diet-induced liver fibrosis reduced the pro-inflammatory response of splenocytes.

Treatment of liver fibrosis is very limited as there is currently no effective anti-fibrotic therapy. Spirulina platensis (SP) is a blue-green alga that is widely supplemented in healthy foods. The objective of this study was to determine whether SP supplementation can prevent obesity-induced liver fibrosis in vivo. Male C57BL/6J mice were randomly assigned to a low-fat or a high-fat (HF)/high-sucrose/high-cholesterol diet or an HF diet supplemented with 2·5 % SP (w/w) (HF/SP) for 16 or 20 weeks. There were no significant differences in body weight, activity, energy expenditure, serum lipids or glucose tolerance between mice on HF and HF/SP diets. However, plasma alanine aminotransferase level was significantly reduced by SP at 16 weeks. Expression of fibrotic markers and trichrome stains showed no differences between HF and HF/SP. Splenocytes isolated from HF/SP fed mice had lower inflammatory gene expression and cytokine secretion compared with splenocytes from HF-fed mice. SP supplementation did not attenuate HF-induced liver fibrosis. However, the expression and secretion of inflammatory genes in splenocytes were significantly reduced by SP supplementation, demonstrating the anti-inflammatory effects of SP in vivo. Although SP did not show appreciable effect on the prevention of liver fibrosis in this mouse model, it may be beneficial for other inflammatory conditions.