scholarly journals Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Angelina Mouralidarane ◽  
Junpei Soeda ◽  
Clara Visconti-Pugmire ◽  
Anne-Maj Samuelsson ◽  
Joaquim Pombo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Immune Dysfunction ◽  
Innate Immune ◽  
Nonalcoholic Fatty Liver

scholarly journals Oxidative stress and altered lipid homeostasis in the programming of offspring fatty liver by maternal obesity

2014 ◽  
Vol 307 (1) ◽  
pp. R26-R34 ◽  
Author(s):  
Maria Z. Alfaradhi ◽  
Denise S. Fernandez-Twinn ◽  
Malgorzata S. Martin-Gronert ◽  
Barbara Musial ◽  
Abigail Fowden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Later Life ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver

Changes in the maternal nutritional environment during fetal development can influence offspring's metabolic risk in later life. Animal models have demonstrated that offspring of diet-induced obese dams develop metabolic complications, including nonalcoholic fatty liver disease. In this study we investigated the mechanisms in young offspring that lead to the development of nonalcoholic fatty liver disease (NAFLD). Female offspring of C57BL/6J dams fed either a control or obesogenic diet were studied at 8 wk of age. We investigated the roles of oxidative stress and lipid metabolism in contributing to fatty liver in offspring. There were no differences in body weight or adiposity at 8 wk of age; however, offspring of obese dams were hyperinsulinemic. Oxidative damage markers were significantly increased in their livers, with reduced levels of the antioxidant enzyme glutathione peroxidase-1. Mitochondrial complex I and II activities were elevated, while levels of mitochondrial cytochrome c were significantly reduced and glutamate dehydrogenase was significantly increased, suggesting mitochondrial dysfunction. Offspring of obese dams also had significantly greater hepatic lipid content, associated with increased levels of PPARγ and reduced triglyceride lipase. Liver glycogen and protein content were concomitantly reduced in offspring of obese dams. In conclusion, offspring of diet-induced obese dams have disrupted liver metabolism and develop NAFLD prior to any differences in body weight or body composition. Oxidative stress may play a mechanistic role in the progression of fatty liver in these offspring.

scholarly journals Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Minglan Li ◽  
Clare M. Reynolds ◽  
Stephanie A. Segovia ◽  
Clint Gray ◽  
Mark H. Vickers
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Early Life ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Later Life ◽  
Developmental Programming ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk

Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.

scholarly journals Transgenerational impact of maternal obesogenic diet on offspring bile acid homeostasis and nonalcoholic fatty liver disease

2019 ◽  
Vol 316 (4) ◽  
pp. E674-E686 ◽  
Author(s):  
Michael D. Thompson ◽  
Alaina Derse ◽  
Jeremie LA Ferey ◽  
Michaela Reid ◽  
Yan Xie ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Maternal Obesity ◽  
Maternal Diet ◽  
Nonalcoholic Fatty Liver ◽  
Periportal Fibrosis

Studies show maternal obesity is a risk factor for metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in offspring. Here we evaluated potential mechanisms underlying these phenotypes. Female C57Bl6 mice were fed chow or an obesogenic high-fat/high-sucrose (HF/HS) diet with subsequent mating of F1 and F2 female offspring to lean males to develop F2 and F3 generations, respectively. Offspring were fed chow or fibrogenic (high transfat, cholesterol, fructose) diets, and histopathological, metabolic changes, and bile acid (BA) homeostasis was evaluated. Chow-fed F1 offspring from maternal HF/HS lineages (HF/HS) developed periportal fibrosis and inflammation with aging, without differences in hepatic steatosis but increased BA pool size and shifts in BA composition. F1, but not F2 or F3, offspring from HF/HS showed increased steatosis on a fibrogenic diet, yet inflammation and fibrosis were paradoxically decreased in F1 offspring, a trend continued in F2 and F3 offspring. HF/HS feeding leads to increased periportal fibrosis and inflammation in chow-fed offspring without increased hepatic steatosis. By contrast, fibrogenic diet-fed F1 offspring from HF/HS dams exhibited worse hepatic steatosis but decreased inflammation and fibrosis. These findings highlight complex adaptations in NAFLD phenotypes with maternal diet.

scholarly journals The Role of Innate Immune Cells in Nonalcoholic Fatty Liver Disease

2021 ◽  
pp. 1-11
Author(s):  
Marina Nati ◽  
Kyoung-Jin Chung ◽  
Triantafyllos Chavakis
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Immune Cell ◽  
Innate Immune ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Recent Developments ◽  
Macrophage Populations

Nonalcoholic fatty liver disease (NAFLD) is a very common hepatic pathology featuring steatosis and is linked to obesity and related conditions, such as the metabolic syndrome. When hepatic steatosis is accompanied by inflammation, the disorder is defined as nonalcoholic steatohepatitis (NASH), which in turn can progress toward fibrosis development that can ultimately result in cirrhosis. Cells of innate immunity, such as neutrophils or macrophages, are central regulators of NASH-related inflammation. Recent studies utilizing new experimental technologies, such as single-cell RNA sequencing, have revealed substantial heterogeneity within the macrophage populations of the liver, suggesting distinct functions of liver-resident Kupffer cells and recruited monocyte-derived macrophages with regards to regulation of liver inflammation and progression of NASH pathogenesis. Herein, we discuss recent developments concerning the function of innate immune cell subsets in NAFLD and NASH.

Innate Immune Signaling in Nonalcoholic Fatty Liver Disease and Cardiovascular Diseases

2019 ◽  
Vol 14 (1) ◽  
pp. 153-184 ◽  
Author(s):  
Jingjing Cai ◽  
Meng Xu ◽  
Xiaojing Zhang ◽  
Hongliang Li
Keyword(s):  
Liver Disease ◽  
Cardiovascular Diseases ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Diseases ◽  
Innate Immune ◽  
Immune Signaling ◽  
Nonalcoholic Fatty Liver ◽  
Innate Immune Signaling

The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival. In addition, emerging evidence from the study of immunometabolism indicates that the systemic metabolic status may have profound effects on cellular immune function and phenotypes through the alteration of cell-intrinsic metabolism. We summarize how the innate immune system interacts with metabolic disturbances to trigger immune-dependent and immune-independent pathogenesis in the context of nonalcoholic fatty liver disease, as representative of metabolic diseases, and cardiovascular diseases.

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