scholarly journals Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease

2020 ◽  
Vol 21 (23) ◽  
pp. 9156
Author(s):  
Rachel B. Wilson ◽  
Richard Zhang ◽  
Yun Jin Chen ◽  
Kia M. Peters ◽  
Cynthia G. Sawyez ◽  
...  

Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD.

2021 ◽  
Vol 12 ◽  
pp. 204201882110002
Author(s):  
Taeang Arai ◽  
Masanori Atsukawa ◽  
Akihito Tsubota ◽  
Shigeru Mikami ◽  
Hiroki Ono ◽  
...  

Background: Although sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve not only glycemic control but also liver inflammation and fatty changes in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), its sustainability and effect on liver fibrosis have remained unclear. The current study aimed to clarify the effects of 48-week SGLT2-I therapy on liver inflammation, fatty changes, and fibrosis in NAFLD patients with T2DM. Methods: This study evaluated the effects of SGLT2-I on NAFLD, including liver fibrosis assessed via transient elastography, in 56 patients with NAFLD who received SGLT2-I for 48 weeks. Moreover, changes in each clinical parameter between patients receiving SGLT2-I (the SGLT2-I group) and those receiving other oral hypoglycemic agents (OHAs) (the non-SGLT2-I group) were compared, using 1:1 propensity score matching to adjust for baseline factors. Results: The SGLT2-I group exhibited a significant decrease in controlled attenuation parameter (312 dB/m at baseline to 280 dB/m at week 48) and liver stiffness measurement (9.1–6.7 kPa) ( p < 0.001 for both). After propensity score matching (44 patients each in the SGLT2-I and non-SGLT2-I groups), no significant difference in HbA1c decrease was observed between the two groups. However, compared with the non-SGLT2-I group, the SGLT2-I group showed a significant decrease in body weight ( p < 0.001), alanine aminotransferase ( p = 0.02), uric acid ( p < 0.001), and Fibrosis-4 (FIB-4) index ( p = 0.01) at week 48. The improvement in FIB-4 index, defined as a ⩾10% decline from baseline at week 48, was 56.8% (25/44) in the SGLT2-I group and 20.5% (9/44) in the non-SGLT2-I group ( p < 0.001). Conclusion: SGLT2-Is improved not only glycemic control but also liver fatty infiltration and fibrosis in patients with NAFLD and T2DM, suggesting their possible superiority to other OHAs concerning these effects.


2021 ◽  
Vol 8 (1) ◽  
pp. e000634
Author(s):  
Monica A Tincopa ◽  
Jane Wong ◽  
Michael Fetters ◽  
Anna S Lok

ObjectiveDespite clear evidence that weight loss via nutritional and physical activity changes improves histological outcomes in non-alcoholic fatty liver disease (NAFLD), many patients struggle to implement and maintain these health behaviour changes. The aim of this study was to characterise disease knowledge, attitudes and behaviours among persons with NAFLD and to identify the factors driving these health behaviours and perceptions.DesignWe conducted semistructured interviews among patients with NAFLD. We used purposeful sampling to enroll equivalent percentages based on age and sex, and enrolled approximately one-third of patients with cirrhosis to capture those perspectives. Interviews were conducted until thematic saturation was achieved. Transcripts were coded using NVivo software to identify themes and subthemes.ResultsA total of 29 patient interviews were completed. Ambiguity about the diagnosis and aetiology of their liver disease was a key theme, though the vast majority of patients were aware that weight loss via nutrition and exercise was the primary therapy. Most patients were asymptomatic, diagnosed incidentally, and reported low level of concern regarding their diagnosis. The primary barriers and facilitators to health behaviour change were the presence of social support, competing medical comorbidities and low motivation to change behaviours.ConclusionsAlthough patients are aware that lifestyle interventions are the primary therapy for NAFLD, there is a gap in knowledge about the condition. The presence of social support and competing medical comorbidities were the most consistent facilitators and barriers to lifestyle change. Tailoring treatment recommendations to provide relevant disease education, specific nutrition and exercise regimens, and personalised approaches based on specific individual barriers and facilitators will likely aid in uptake and maintenance of first-line therapy for NAFLD.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Deirdre Ní Fhloinn ◽  
Ciara Wright ◽  
Sara Naimimohasses ◽  
Stephen Finn ◽  
Suzanne Norris ◽  
...  

AbstractNon-alcoholic fatty liver disease (NAFLD) is a significant public health concern closely linked to obesity, affecting an estimated 25% of adults in Europe. Understudied in Ireland, the aim of this research was to examine the effects of a 12-week multi-component dietary intervention on weight loss and markers of liver injury in Irish NAFLD patients in tertiary care. Biopsy confirmed NAFLD patients (n = 27) were recruited from St James’ Hospital in Dublin, Ireland. Consenting participants underwent a 12-week moderate-intensity intervention incorporating weekly group nutritional education, behavioural change and group support, as well as individualised advice and weigh-ins from a trained nutritionist. Control group participants were given routine clinical care. All participants were clinically reviewed before, immediately after, and 3 months post intervention. Individuals (n = 12) with histological evidence of steatohepatitis underwent a repeat liver biopsy on completion of the intervention. Detailed dietary assessment was performed using both a 4-day diet diary (4DDD) and a novel, recently validated, short food frequency questionnaire (SFFQ) designed specifically to assess habitual intakes of food items related to NAFLD. Nutrient intakes were analysed using myFood24TM dietary analysis software, and the Mediterranean diet quality score (MDQS) was used to assess the overall change in dietary patterns. Of the 15 participants who completed the intervention, 80% (n = 12) achieved a weight loss exceeding 5%, with 47% (n = 7) achieving > 7%. There were significant improvements from baseline to week 12 in the intervention group for the majority of clinical parameters including HbA1c (p = 0.0054), liver enzymes (ALT, p = 0.0108; GGT, p = 0.0001) and transient elastography (kPA, p = 0.0308; CAP, p = 0.0081). However, these results failed to maintain significance when analysed compared to controls. The overall dietary pattern was significantly improved after 12 weeks as assessed by the MDQS (p = 0.03), with no apparent compromise in micronutrient intake despite the energy reduction. Reductions in energy, saturated fat, carbohydrate and sugar intakes at 12 weeks, were maintained at three months follow up. Analysis of pre- and post-intervention liver biopsies in the intervention group demonstrated a clinically significant improvement in NAS score (p = 0.0273), attributable to reductions in hepatic steatosis (p = 0.0078). A significant correlation was observed between improvement in liver histology and change in sugar intake (r = 0.7534, p = 0.0093). Although results were somewhat limited by small sample size, nutritional education achieved beneficial dietary changes that persisted after the intervention ceased. Notably, achieving reductions in sugar intakes may be particularly beneficial in reducing the severity of hepatic steatosis in Irish adults with NAFLD.


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