scholarly journals Dynamics of hepatic steatosis resolution and changes in gut microbiome with weight loss in nonalcoholic fatty liver disease

2021 ◽  
Author(s):  
Jaideep Behari ◽  
Lisa Graham ◽  
Renwei Wang ◽  
Claudiu Schirda ◽  
Amir A. Borhani ◽  
...  
2017 ◽  
Vol 38 (5) ◽  
pp. 924-931 ◽  
Author(s):  
Page Axley ◽  
Sudha Kodali ◽  
Yong-Fang Kuo ◽  
Sujan Ravi ◽  
Toni Seay ◽  
...  

2014 ◽  
Vol 306 (6) ◽  
pp. G496-G504 ◽  
Author(s):  
Akihiro Asai ◽  
Pauline M. Chou ◽  
Heng-Fu Bu ◽  
Xiao Wang ◽  
M. Sambasiva Rao ◽  
...  

Liver steatosis in nonalcoholic fatty liver disease is affected by genetics and diet. It is associated with insulin resistance (IR) in hepatic and peripheral tissues. Here, we aimed to characterize the severity of diet-induced steatosis, obesity, and IR in two phylogenetically distant mouse strains, C57BL/6J and DBA/2J. To this end, mice (male, 8 wk old) were fed a high-fat and high-carbohydrate (HFHC) or control diet for 16 wk followed by the application of a combination of classic physiological, biochemical, and pathological studies to determine obesity and hepatic steatosis. Peripheral IR was characterized by measuring blood glucose level, serum insulin level, homeostasis model assessment of IR, glucose intolerance, insulin intolerance, and AKT phosphorylation in adipose tissues, whereas the level of hepatic IR was determined by measuring insulin-triggered hepatic AKT phosphorylation. We discovered that both C57BL/6J and DBA/2J mice developed obesity to a similar degree without the feature of liver inflammation after being fed an HFHC diet for 16 wk. C57BL/6J mice in the HFHC diet group exhibited severe pan-lobular steatosis, a marked increase in hepatic triglyceride levels, and profound peripheral IR. In contrast, DBA/2J mice in the HFHC diet group developed only a mild degree of pericentrilobular hepatic steatosis that was associated with moderate changes in peripheral IR. Interestingly, both C57BL/6J and DBA/2J developed severe hepatic IR after HFHC diet treatment. Collectively, these data suggest that the severity of diet-induced hepatic steatosis is correlated to the level of peripheral IR, not with the severity of obesity and hepatic IR. Peripheral rather than hepatic IR is a dominant factor of pathophysiology in nonalcoholic fatty liver disease.


2018 ◽  
Vol 40 (2) ◽  
pp. 417-446 ◽  
Author(s):  
Mathis Grossmann ◽  
Margaret E Wierman ◽  
Peter Angus ◽  
David J Handelsman

Abstract The liver and the reproductive system interact in a multifaceted bidirectional fashion. Sex steroid signaling influences hepatic endobiotic and xenobiotic metabolism and contributes to the pathogenesis of functional and structural disorders of the liver. In turn, liver function affects the reproductive axis via modulating sex steroid metabolism and transport to tissues via sex hormone–binding globulin (SHBG). The liver senses the body’s metabolic status and adapts its energy homeostasis in a sex-dependent fashion, a dimorphism signaled by the sex steroid milieu and possibly related to the metabolic costs of reproduction. Sex steroids impact the pathogenesis of nonalcoholic fatty liver disease, including development of hepatic steatosis, fibrosis, and carcinogenesis. Preclinical studies in male rodents demonstrate that androgens protect against hepatic steatosis and insulin resistance both via androgen receptor signaling and, following aromatization to estradiol, estrogen receptor signaling, through regulating genes involved in hepatic lipogenesis and glucose metabolism. In female rodents in contrast to males, androgens promote hepatic steatosis and dysglycemia, whereas estradiol is similarly protective against liver disease. In men, hepatic steatosis is associated with modest reductions in circulating testosterone, in part consequent to a reduction in circulating SHBG. Testosterone treatment has not been demonstrated to improve hepatic steatosis in randomized controlled clinical trials. Consistent with sex-dimorphic preclinical findings, androgens promote hepatic steatosis and dysglycemia in women, whereas endogenous estradiol appears protective in both men and women. In both sexes, androgens promote hepatic fibrosis and the development of hepatocellular carcinoma, whereas estradiol is protective.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Doo Jin Choi ◽  
Seong Cheol Kim ◽  
Gi Eun Park ◽  
Bo-Ram Choi ◽  
Dae Young Lee ◽  
...  

The present study aimed to evaluate the potential synergistic and protective effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extract in a ratio of 7 : 3, against hepatic steatosis in high fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) mice. Forty-eight mice were randomly divided into eight groups and orally administered daily for 6 weeks with a normal diet (ND) or high fat diet alone (HFD), HFD with AM (HFD + 100 mg/kg AM extract), HFD with LE (HFD + 100 mg/kg LE extract), HFD with ALM16 (HFD + 50, 100, and 200 mg/kg ALM16), or HFD with MT (HFD + 100 mg/kg Milk thistle extract) as a positive control. ALM16 significantly decreased the body and liver weight, serum and hepatic lipid profiles, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL), and low-density lipoprotein-cholesterol (LDL), and serum glucose levels, compared to the HFD group. Moreover, ALM16 significantly ameliorated the HFD-induced increased hepatic injury markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT)-1. Furthermore, as compared to the mice fed HFD alone, ALM16 increased the levels of phosphorylated AMP-activated protein kinase (p-AMPK) and acetyl-CoA carboxylase (p-ACC), thereby upregulating the expression of carnitine palmitoyltransferase (CPT)-1 and downregulating the expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS). These results demonstrated that ALM16 markedly inhibited HFD-induced hepatic steatosis in NAFLD mice by modulating AMPK and ACC signaling pathways, and may be more effective than the single extracts of AM or LE.


Radiology ◽  
2020 ◽  
Vol 295 (1) ◽  
pp. 106-113 ◽  
Author(s):  
Aiguo Han ◽  
Yingzhen N. Zhang ◽  
Andrew S. Boehringer ◽  
Vivian Montes ◽  
Michael P. Andre ◽  
...  

2019 ◽  
Vol 25 (11) ◽  
pp. e146-e147 ◽  
Author(s):  
Mitsuro Chiba ◽  
Kunio Nakane ◽  
Hitoshi Abe ◽  
Masafumi Komatsu ◽  
Haruhiko Tozawa

Abstract Nonalcoholic fatty liver disease (NAFLD) develops in ulcerative colitis (UC) and Crohn’s disease. However, there is scarce reporting on the onset of UC in patients with NAFLD. A 44-year-old man was diagnosed with UC and referred to us in 2019. His height was 166.0 cm, and body weight was 86.3 kg. The waist circumference was 93.7 cm (normal range <85) and triglyceride was 751 mg/dL. These findings, in addition to hypertension, resulted in a diagnosis of metabolic syndrome. HbA1c was normal. Ultrasonography disclosed severe fatty liver. Nonalcoholic fatty liver disease was diagnosed. He underwent 12 days of educational hospitalization for UC. A lacto-ovo-semi-vegetarian diet (1400 kcal/day), a kind of plant-based diet (PBD), was provided. He lost 4 kg, which was 4.6% of his base body weight. Triglyceride and total cholesterol decreased to the normal ranges. Transaminases and γ-glutamyl transpeptidase also decreased. His body weight decreased further after discharge. Follow-up ultrasonography indicated an improvement in hepatic enlargement. The shear wave velocity decreased from 1.11 to 0.88 m/s. His soft stool became normal stool by 2 months after discharge. Records of his health checkups revealed the presence of metabolic syndrome and abnormal liver function tests already in 2015. Thus, it was concluded that UC developed in a patient with NAFLD in this case. Plant-based diet has already been shown to be effective in inflammatory bowel disease (IBD). In the present case, NAFLD parameters were dramatically improved by PBD. Whether the improvement was due to weight loss per se or due to weight loss with PBD is to be clarified.


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