scholarly journals Deficiency in Tissue Non-Specific Alkaline Phosphatase Leads to Steatohepatitis in Mice Fed a High Fat Diet Similar to That Produced by a Methionine and Choline Deficient Diet

2020 ◽  
Vol 22 (1) ◽  
pp. 51
Author(s):  
Reyes Gámez-Belmonte ◽  
Mireia Tena-Garitaonaindia ◽  
Cristina Hernández-Chirlaque ◽  
Samir Córdova ◽  
Diego Ceacero-Heras ◽  
...  
Keyword(s):  
Weight Loss ◽  
Alkaline Phosphatase ◽  
Hepatic Steatosis ◽  
Plasma Levels ◽  
Control Diet ◽  
Bile Secretion ◽  
Standard Diet ◽  
Deficient Diet ◽  
No Weight Loss

The liver expresses tissue-nonspecific alkaline phosphatase (TNAP), which may participate in the defense against bacterial components, in cell regulation as part of the purinome or in bile secretion, among other roles. We aimed to study the role of TNAP in the development of hepatosteatosis. TNAP+/− haplodeficient and wild type (WT) mice were fed a control diet (containing 10% fat w/w) or the same diet deficient in methionine and choline (MCD diet). The MCD diet induced substantial weight loss together with hepatic steatosis and increased alanine aminotransferase (ALT) plasma levels, but no differences in IL-6, TNF, insulin or resistin. There were no substantial differences between TNAP+/− and WT mice fed the MCD diet. In turn, TNAP+/− mice receiving the control diet presented hepatic steatosis with alterations in metabolic parameters very similar to those induced by the MCD diet. Nevertheless, no weight loss, increased ALT plasma levels or hypoglycemia were observed. These mice also presented increased levels of liver TNF and systemic resistin and glucagon compared to WT mice. The phenotype of TNAP+/− mice fed a standard diet was normal. In conclusion, TNAP haplodeficiency induces steatosis comparable to that produced by a MCD diet when fed a control diet.

Role of prolactin in vitamin D metabolism and calcium absorption during lactation in the rat

1982 ◽  
Vol 94 (3) ◽  
pp. 443-453 ◽  
Author(s):  
C. J. Robinson ◽  
E. Spanos ◽  
M. F. James ◽  
J. W. Pike ◽  
M. R. Haussler ◽  
...  
Keyword(s):  
Vitamin D ◽  
Alkaline Phosphatase ◽  
Parathyroid Hormone ◽  
Alkaline Phosphatase Activity ◽  
Plasma Levels ◽  
Calcium Absorption ◽  
High Plasma ◽  
Intestinal Calcium Absorption ◽  
Vitamin D Metabolism

Intestinal calcium absorption and plasma levels of 1,25-dihydroxycholecalciferol (1,25(OH)2D3) were measured in lactating and non-lactating rats and the effects of bromocriptine and exogenous prolactin treatment were evaluated. In lactating rats calcium absorption and plasma levels of parathyroid hormone, 1,25(OH)2D3 and alkaline phosphatase activity were significantly increased. Bromocriptine treatment significantly reduced the enhanced calcium absorption and levels of plasma 1,25(OH)2D3 and alkaline phosphatase but had no significant effect on plasma levels of parathyroid hormone. Prolactin administered with bromocriptine to lactating animals prevented all the changes observed with bromocriptine treatment alone. It was concluded that the increased plasma levels of prolactin during lactation lead to high plasma levels of 1,25(OH)2D3 which are responsible for the enhanced intestinal calcium absorption.

scholarly journals The Intestinal Microbiome Predicts Weight Loss on a Calorie-Restricted Diet and Is Associated With Improved Hepatic Steatosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Tien S. Dong ◽  
Kayti Luu ◽  
Venu Lagishetty ◽  
Farzaneh Sedighian ◽  
Shih-Lung Woo ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Clinical Response ◽  
Hepatic Steatosis ◽  
Calorie Restriction ◽  
Intestinal Microbiome ◽  
Composition Analysis ◽  
Rrna Gene ◽  
Restricted Diet

Background: The microbiome has been shown in pre-clinical and epidemiological studies to be important in both the development and treatment of obesity and metabolic associated fatty liver disease (MAFLD). However, few studies have examined the role of the microbiome in the clinical response to calorie restriction. To explore this area, we performed a prospective study examining the association of the intestinal microbiome with weight loss and change in hepatic steatosis on a calorie-restricted diet.Methods: A prospective dietary intervention study of 80 overweight and obese participants was performed at the Greater West Los Angeles Veterans Affair Hospital. Patients were placed on a macronutrient standardized diet for 16 weeks, including 14 weeks of calorie restriction (500 calorie deficit). Body composition analysis by impedance, plasma lipid measurements, and ultrasound elastography to measure hepatic steatosis were performed at baseline and week 16. Intestinal microbiome composition was assessed using 16S rRNA gene sequencing. A per protocol analysis was performed on all subjects completing the trial (n = 46).Results: Study completers showed significant reduction in weight, body mass index, total cholesterol, low density lipoprotein, and triglyceride. Subjects who lost at least 5% of their body weight had significantly greater reduction in serum triglyceride and hepatic steatosis than those with <5% body weight loss. Enterococcus and Klebsiella were reduced at the end of the trial while Coprococcus and Collinsella were increased. There were also significant baseline microbiome differences between patients who had at least 5% weight loss as compared to those that did not. Lachnoclostridium was positively associated with hepatic steatosis and Actinomyces was positively associated with hepatic steatosis and weight. Baseline microbiome profiles were able to predict which patients lost at least 5% of their body weight with an AUROC of 0.80.Conclusion: Calorie restriction alters the intestinal microbiome and improves hepatic steatosis in those who experience significant weight loss. Baseline microbiome differences predict weight loss on a calorie–restricted diet and are associated with improvement in hepatic steatosis, suggesting a role of the gut microbiome in mediating the clinical response to calorie restriction.

scholarly journals Dietary and Genetic Cholesterol Loading Rather Than Steatosis Promotes Liver Tumorigenesis and NASH-Driven HCC

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4091
Author(s):  
Vicent Ribas ◽  
Laura Conde de la Rosa ◽  
David Robles ◽  
Susana Núñez ◽  
Paula Segalés ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Liver Tumors ◽  
Tumor Promoter ◽  
Immune Checkpoints ◽  
High Cholesterol Diet ◽  
Chow Diet ◽  
High Fat ◽  
Deficient Diet ◽  
Lipid Species

The association of nonalcoholic steatohepatitis (NASH) with obesity and type 2 diabetes is a major determinant factor for the continued rise of NASH-driven HCC. Unfortunately, the mechanisms underlying the progression from NASH to HCC are not well-understood. Steatosis is characterized by the accumulation of different lipid species, and cholesterol has emerged as an important player in NASH development, which has been shown to promote NASH-driven HCC. However, recent findings indicated a tumor suppressor role of cholesterol in liver carcinogenesis and HCC development. Thus, we examined the contribution of hepatic steatosis with or without cholesterol accumulation induced by dietary or genetic approaches in liver tumorigenesis and whether the role of cholesterol in NASH-driven HCC is species-dependent. While diethylnitrosamine (DEN) treatment to rats or mice fed a choline-deficient diet decreased the hepatic steatosis, feeding an atherogenic diet enriched in cholesterol potentiated the liver tumor markers. Similar effects were observed in DEN-treated transgenic SREBP-2 mice but not wild-type (WT) mice fed a regular chow diet. Remarkably, long-term feeding of a high-fat high-cholesterol diet (HFHC) but not a high-fat diet (HFD) to WT mice caused severe NASH with spontaneous progression to HCC. A similar outcome was observed in MUP-uPA transgenic mice fed a HFHC diet, which resulted in increased liver tumors and expression of the genes involved in the immune checkpoints. Ezetimibe treatment ameliorated chronic liver disease and, more importantly, tumor multiplicity in HFHC-fed MUP-uPA mice or DEN-treated WT mice. Thus, these results revealed a differential role of steatosis and cholesterol in NASH-driven HCC and indicated that the tumor-promoter role of cholesterol is species-independent and associated with impaired immunosurveillance.

Dietary nitrate metabolism and enteric methane mitigation in sheep consuming a protein-deficient diet

2020 ◽  
Vol 60 (2) ◽  
pp. 232
Author(s):  
L. Villar ◽  
R. Hegarty ◽  
M. Van Tol ◽  
I. Godwin ◽  
J. Nolan
Keyword(s):  
Volatile Fatty Acids ◽  
Control Diet ◽  
Animal Performance ◽  
Deficient Diet ◽  
Ch4 Emissions ◽  
Enteric Methane ◽  
Designed Experiment ◽  
Protein Deficient Diet ◽  
Nitrate Metabolism

It was hypothesised that the inclusion of nitrate (NO3–) or cysteamine hydrochloride (CSH) in a protein deficient diet (4.8% crude protein; CP) would improve the productivity of sheep while reducing enteric methane (CH4) emissions. A complete randomised designed experiment was conducted with yearling Merino sheep (n = 24) consuming a protein-deficient wheaten chaff control diet (CON) alone or supplemented with 1.8% nitrate (NO3–; DM basis), 0.098% urea (Ur, DM basis) or 80 mg cysteamine hydrochloride/kg liveweight (CSH). Feed intake, CH4 emissions, volatile fatty acids (VFA), digesta kinetics and NO3–, nitrite (NO2–) and urea concentrations in plasma, saliva and urine samples were measured. There was no dietary effect on animal performance or digesta kinetics (P > 0.05), but adding NO3– to the CON diet reduced methane yield (MY) by 26% (P = 0.01). Nitrate supplementation increased blood MetHb, plasma NO3– and NO2– concentrations (P < 0.05), but there was no indication of NO2– toxicity. Overall, salivary NO3– concentration was greater than plasma NO3– (P < 0.05), indicating that NO3– was concentrated into saliva. Our results confirm the role of NO3– as an effective additive to reduce CH4 emissions, even in a highly protein-deficient diet and as a source of additional nitrogen (N) for microbial protein synthesis via N-recycling into saliva and the gut. The role of CSH as an additive in low quality diets for improving animal performance and reducing CH4 emissions is still unclear.

scholarly journals The Role of Gut Microbiota in Duodenal-Jejunal Bypass Surgery-Induced Improvement of Hepatic Steatosis in HFD-Fed Rats

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Gao ◽  
Jia Zhang ◽  
Xiao Xiao ◽  
Yifan Ren ◽  
Xiaopeng Yan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
Bypass Surgery ◽  
Fecal Microbiota ◽  
Standard Diet ◽  
Sham Operation ◽  
Fecal Transplant ◽  
Male Adult ◽  
Jejunal Bypass

Bariatric surgery including duodenal-jejunal bypass surgery (DJB) improves insulin sensitivity and reduces obesity-associated inflammation. However, the underlying mechanism for such an improvement is still incompletely understood. Our objective was to investigate the role of the gut microbiota in DJB-associated improvement of hepatic steatosis in high fat diet (HFD)-fed rats. To study this, hepatic steatosis was induced in male adult Sprague-Dawley rats by feeding them with a 60% HFD. At 8 weeks after HFD feeding, the rats were subjected to either DJB or sham operation. HFD was resumed 1 week after the surgery for 3 more weeks. In additional groups of animals, feces were collected from HFD-DJB rats at 2 weeks after DJB. These feces were then transplanted to HFD-fed rats without DJB at 8 weeks after HFD feeding. Hepatic steatosis and fecal microbiota were analyzed at 4 weeks after surgery or fecal transplantation. Our results showed that DJB alleviated hepatic steatosis in HFD-fed rats. Fecal microbiota analysis showed that HFD-fed and standard diet-fed rats clustered differently. DJB induced substantial compositional changes in the gut microbiota. The fecal microbiota of HFD-fed rats received fecal transplant from DJB rats overlapped with that of HFD-DJB rats. Treatment of rats with HFD-induced liver lesions by fecal transplant from DJB-operated HFD-fed rats also attenuated hepatic steatosis. Thus, alterations in the gut microbiota after DJB surgery are sufficient to attenuate hepatic steatosis in HFD-fed rats. Targeting the gut microbiota could be a promising approach for preventing or treating human NAFLD.

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice

2014 ◽  
Vol 306 (5) ◽  
pp. E552-E558 ◽  
Author(s):  
Johanne H. Ellenbroek ◽  
Laura van Dijck ◽  
Hendrica A. Töns ◽  
Ton J. Rabelink ◽  
Françoise Carlotti ◽  
...  
Keyword(s):  
Weight Loss ◽  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
Cell Mass ◽  
High Fat ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
No Weight Loss ◽  
Low Carbohydrate

High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown. In this study we investigate the effects of long-term KD on glucose tolerance and β- and α-cell mass in mice. Despite an initial weight loss, KD did not result in weight loss after 22 wk. Plasma markers associated with dyslipidemia and inflammation (cholesterol, triglycerides, leptin, monocyte chemotactic protein-1, IL-1β, and IL-6) were increased, and KD-fed mice showed signs of hepatic steatosis after 22 wk of diet. Long-term KD resulted in glucose intolerance that was associated with insufficient insulin secretion from β-cells. After 22 wk, insulin-stimulated glucose uptake was reduced. A reduction in β-cell mass was observed in KD-fed mice together with an increased number of smaller islets. Also α-cell mass was markedly decreased, resulting in a lower α- to β-cell ratio. Our data show that long-term KD causes dyslipidemia, a proinflammatory state, signs of hepatic steatosis, glucose intolerance, and a reduction in β- and α-cell mass, but no weight loss. This indicates that long-term high-fat, low-carbohydrate KD lead to features that are also associated with the metabolic syndrome and an increased risk for type 2 diabetes in humans.

scholarly journals The vitamin E reduces liver lipoperoxidation and fibrosis in a model of nonalcoholic steatohepatitis

2010 ◽  
Vol 47 (1) ◽  
pp. 86-92 ◽  
Author(s):  
Idilio Zamin Jr ◽  
Angelo Alves de Mattos ◽  
Ângelo Zambam de Mattos ◽  
Gabriela Coral ◽  
Diogo Santos ◽  
...  
Keyword(s):  
Vitamin E ◽  
Nonalcoholic Steatohepatitis ◽  
Wistar Rats ◽  
Biochemical Analysis ◽  
Diet Group ◽  
Standard Diet ◽  
Deficient Diet ◽  
Simvastatin Group ◽  
Standard Diet Group

CONTEXT: No effective treatment is available for nonalcoholic steatohepatitis in nowadays. OBJECTIVES: To develop a model of nonalcoholic steatohepatitis induced by a methionine and choline deficient diet, as well as to evaluate the role of metformin, vitamin E and simvastatin in the nonalcoholic steatohepatitis progression. METHODS: The study analyzed prospectively 50 Wistar rats for a 90-day period and divided them into five groups of 10 rats. One group was given standard rat diet and the others received the methionine and choline deficient diet. Among the four groups that received this diet, one received saline 0,9% and the others received metformin, vitamin E or simvastatin. After the study period, the animals were sacrificed and their blood was collected for biochemical analysis. The livers were removed for lipoperoxidation analysis and for the histological examinations. RESULTS: The methionine and choline deficient diet was able to induce steatosis in 100% of the animals and nonalcoholic steatohepatitis in 27 (69.2%). The alanine aminotransferase levels were significantly higher in the simvastatin group. The aspartate aminotransferase levels were also higher in the simvastatin group, but were statistically significant only in relation to the standard diet group. When lipoperoxidation values were compared, the groups that received standard rat diet and methionine and choline deficient with vitamin E presented significantly lower rates than the others. The presence of fibrosis was significantly smaller in the group receiving vitamin E. CONCLUSIONS: The diet used was able to induce steatosis and nonalcoholic steatohepatitis. Besides vitamin E showed to reduce the liver oxidative stress, as well as the fibrosis development

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

2006 ◽  
Vol 76 (3) ◽  
pp. 111-116 ◽  
Author(s):  
Hiroshi Matsuzaki ◽  
Misao Miwa
Keyword(s):  
Bone Formation ◽  
Calcium Supplementation ◽  
Control Diet ◽  
Formation Rate ◽  
Dietary Calcium ◽  
Mineral Apposition Rate ◽  
Control Group ◽  
Deficient Diet ◽  
Bone Formation Rate ◽  
Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

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