scholarly journals Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2834 ◽  
Author(s):  
Julie Hviid Klaebel ◽  
Mia Skjødt ◽  
Josephine Skat-Rørdam ◽  
Günaj Rakipovski ◽  
David H. Ipsen ◽  
...  

Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints.

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 808
Author(s):  
Julie Hviid Klaebel ◽  
Günaj Rakipovski ◽  
Birgitte Andersen ◽  
Jens Lykkesfeldt ◽  
Pernille Tveden-Nyborg

Despite the lack of effective pharmacotherapy against nonalcoholic steatohepatitis (NASH) and liver fibrosis, vitamin E (vitE) supplementation and lifestyle modifications are recommended for the management of NASH due to promising clinical results. We recently reported a positive effect of supplementation with 800 IU vitE and atorvastatin on NASH resolution in guinea pigs. In the present study, we investigated the effect of high-dose vitE therapy combined with dietary intervention against progressive NASH and advanced fibrosis in the guinea pig model. Sixty-six guinea pigs received either high-fat (HF) or standard guinea pig chow diet (Control) for 25 weeks. Prior to eight weeks of intervention, HF animals were allocated into groups; dietary intervention (Chow) or dietary intervention with 2000 IU/d vitE supplementation (CvitE). Both Chow and CvitE reduced dyslipidemia, hepatic lipid accumulation and liver weight (p < 0.05), while CvitE further decreased hepatocellular ballooning (p < 0.05). Subanalyses of individual responses within intervention groups showed significant correlation between the hepatic hallmarks of NASH and lipid accumulation vs. inflammatory state (p < 0.05). Collectively, our results indicate that individual differences in sensitivity towards intervention and inflammatory status determine the potential beneficial effect of dietary intervention and high-dose vitE supplementation. Moreover, the study suggests that inflammation is a primary target in NASH treatment.


Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 69
Author(s):  
Josephine Skat-Rørdam ◽  
Kamilla Pedersen ◽  
Gry Freja Skovsted ◽  
Ida Gregersen ◽  
Sara Vangsgaard ◽  
...  

Oxidative stress is directly linked to non-alcoholic fatty liver disease (NAFLD) and the progression to steaotohepatitis (NASH). Thus, a beneficial role of antioxidants in delaying disease progression and/or accelerating recovery may be expected, as corroborated by recommendations of, e.g., vitamin E supplementation to patients. This study investigated the effect of vitamin C deficiency—often resulting from poor diets low in fruits and vegetables and high in fat—combined with/without a change to a low fat diet on NAFLD/NASH phenotype and hepatic transcriptome in the guinea pig NASH model. Vitamin C deficiency per se did not accelerate disease induction. However, the results showed an effect of the diet change on the resolution of hepatic histopathological hallmarks (steatosis, inflammation, and ballooning) (p < 0.05 or less) and indicated a positive effect of a high vitamin C intake when combined with a low fat diet. Our data show that a diet change is important in NASH regression and suggest that a poor vitamin C status delays the reversion towards a healthy hepatic transcriptome and phenotype. In conclusion, the findings support a beneficial role of adequate vitamin C intake in the regression of NASH and may indicate that vitamin C supplementation in addition to lifestyle modifications could accelerate recovery in NASH patients with poor vitamin C status.


1969 ◽  
Vol 99 (4) ◽  
pp. 481-484 ◽  
Author(s):  
D. C. Herting ◽  
M. I. Ludwig ◽  
E. E. Drury
Keyword(s):  
Low Fat ◽  

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2389
Author(s):  
Monica Gianna Giroli ◽  
José Pablo Werba ◽  
Patrizia Risé ◽  
Benedetta Porro ◽  
Angelo Sala ◽  
...  

The Mediterranean diet (MD) prevents cardiovascular disease by different putative mechanisms, including modifications in the blood fatty acid (FA) profile. Polytherapy for secondary cardiovascular prevention might mask the effect of MD on the FA profile. This study was aimed to assess whether MD, in comparison with a low-fat diet (LFD), favorably modifies the blood FA profile in patients with coronary heart disease (CHD) on polytherapy. One hundred and twenty patients with a recent history of coronary stenting, randomized to MD or to LFD, completed 3 months of this open-label dietary intervention study. Diet Mediterranean-ness was evaluated using the Mediterranean Diet Adherence Screener (MeDAS) score. Both diets significantly reduced saturated FA (p < 0.01). Putative favorable changes in total n-3 FA (p = 0.03) and eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA; p = 0.04) were significantly larger with MD than with LFD. At 3 months, in the whole cohort, the MeDAS score correlated inversely with palmitic acid (R = −0.21, p = 0.02), and with palmitoleic acid (R = −0.32, p = 0.007), and positively with total n-3 FA (R = 0.19, p = 0.03), EPA (R = 0.28, p = 0.002), and EPA + DHA (R = 0.21, p = 0.02). In CHD patients on polytherapy, both MD and LFD shift FA blood composition towards a healthier profile, with a more favorable effect of MD on omega−3 levels.


2013 ◽  
Vol 92 (5) ◽  
pp. 1221-1226 ◽  
Author(s):  
L. Prola ◽  
J. Nery ◽  
A. Lauwaerts ◽  
C. Bianchi ◽  
L. Sterpone ◽  
...  

2019 ◽  
Author(s):  
Jessica A Grembi ◽  
Lan H Nguyen ◽  
Thomas D Haggerty ◽  
Christopher D Gardner ◽  
Susan P Holmes ◽  
...  

AbstractBackgroundObesity is a complex global health challenge. Although both low-carbohydrate (low-carb) and low-fat diets can lead to weight loss, there is typically substantial variability in weight and related outcomes for both diet approaches among obese but otherwise healthy adults. Elucidating individual characteristics that might contribute to sustained weight loss is critical to developing effective dietary intervention strategies. We hypothesized that structural differences in the gut microbiota explained some portion of the weight loss variability among people randomized to either a low-carb or low-fat diet, possibly related to its effects on dietary compliance.ResultsOur study included two staggered cohorts of obese adults enrolled in the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study - a randomized clinical trial of either a low-fat or low-carb diet. In the discovery cohort (n=66), 161 pre-diet fecal samples were sequenced in addition to 157 samples collected after 10-weeks of dietary intervention. In the validation cohort (n = 56), 106 pre-diet fecal samples were sequenced. Pre-diet taxonomic features, such as the Prevotella/Bacteroides ratio, correlated to weight loss in the discovery cohort were not confirmed in the validation cohort. The most robust finding in the discovery cohort indicated that gut microbiota plasticity was linked to 12-month weight loss in a diet-dependent manner; subjects with higher sustained weight loss on a low-fat diet had higher pre-diet daily plasticity, whereas those most successful on the low-carb diet had greater microbiota plasticity over 10 weeks of dietary intervention. Unfortunately, because sample frequency and timing was quite different in the validation cohort, the relationship between plasticity and weight loss could not be studied in this group.ConclusionsThese findings suggest the potential importance of gut microbiota plasticity in sustained weight loss. We highlight the importance of evaluating kinetic trends and in assessing reproducibility in studies of the gut microbiota.


2020 ◽  
Vol 111 (6) ◽  
pp. 1127-1136 ◽  
Author(s):  
Gabriela K Fragiadakis ◽  
Hannah C Wastyk ◽  
Jennifer L Robinson ◽  
Erica D Sonnenburg ◽  
Justin L Sonnenburg ◽  
...  

Abstract Background With the rising rates of obesity and associated metabolic disorders, there is a growing need for effective long-term weight-loss strategies, coupled with an understanding of how they interface with human physiology. Interest is growing in the potential role of gut microbes as they pertain to responses to different weight-loss diets; however, the ways that diet, the gut microbiota, and long-term weight loss influence one another is not well understood. Objectives Our primary objective was to determine if baseline microbiota composition or diversity was associated with weight-loss success. A secondary objective was to track the longitudinal associations of changes to lower-carbohydrate or lower-fat diets and concomitant weight loss with the composition and diversity of the gut microbiota. Methods We used 16S ribosomal RNA gene amplicon sequencing to profile microbiota composition over a 12-mo period in 49 participants as part of a larger randomized dietary intervention study of participants consuming either a healthy low-carbohydrate or a healthy low-fat diet. Results While baseline microbiota composition was not predictive of weight loss, each diet resulted in substantial changes in the microbiota 3-mo after the start of the intervention; some of these changes were diet specific (14 taxonomic changes specific to the healthy low-carbohydrate diet, 12 taxonomic changes specific to the healthy low-fat diet) and others tracked with weight loss (7 taxonomic changes in both diets). After these initial shifts, the microbiota returned near its original baseline state for the remainder of the intervention, despite participants maintaining their diet and weight loss for the entire study. Conclusions These results suggest a resilience to perturbation of the microbiota's starting profile. When considering the established contribution of obesity-associated microbiotas to weight gain in animal models, microbiota resilience may need to be overcome for long-term alterations to human physiology. This trial was registered at clinicaltrials.gov as NCT01826591.


Author(s):  
B. L. Soloff ◽  
A. L. Barron ◽  
H. J. White ◽  
R. G. Rank

Chlamydial organisms (specifically C. trachomatis) have been implicated as a frequent cause of genital infection in the human (1). Study of the histo- pathological aspects of such infections has been impeded because of difficulties in obtaining adequate tissue specimens and the lack of a suitable experimental host. In 1964, Murray (2) isolated the causative agent of guinea pig inclusion conjunctivitis which possesses similarities to human inclusion conjunctivitis. This guinea pig organism was found to be a member of the Chlamydia psittaci subgroup and was designated as the Gp-ic agent. Male guinea pigs have been successfully infected with Gp-ic by intraurethral inoculation. Transmission of the infection to the female by sexual contact has been demonstrated (3). We are not aware of any ultrastructural studies to date concerning the development of this agent in genital tissue.Studies in our laboratory have established that, in our guinea pig model, the cervix is the major site of injection.


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