scholarly journals The protective effect of nicotinamide riboside against age-induced hepatic disease in mice

Author(s):  
Xue Han ◽  
Xiaogang Bao ◽  
Qi Lou ◽  
Xian Xie ◽  
Shasang Zhou ◽  
...  

Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.

2019 ◽  
Author(s):  
Xue Han ◽  
Xiaogang Bao ◽  
Qi Lou ◽  
Xian Xie ◽  
Shasang Zhou ◽  
...  

Background & Aims. Aging is one of the key triggers of non-alcoholic fatty liver disease (NAFLD). Yet, the pathomechanism of the age-associated NAFLD is not fully understood. Nicotinamide adenine dinucleotide (NAD), an ubiquitous coenzyme, has beneficial effects on aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of age-induced NAFLD. Methods. NR supplied food (2.5g/kg food) was applied to aged mice for three months. Changes of body weight, food intake, hepar weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammation infiltrated. Results. NR significantly reduced fat pat mass, lipid content and AST in aged mice, but didn't modify in terms of body weight, food intake, hepar weight and ALT in aged mice. Given normal chow, aged mice displayed decline of NAD concentration. In aged mice model, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis (Masson's trichrome staining and TGF-β staining) were observed in liver. In addition, Kupffer cells accumulated and pro-inflammatory cytokines expression were more aggravated in hepatic tissues. Whereas, NR administration completely corrected these NAFLD phenotypes and inflammation infiltrated in liver. Conclusion. NR has benefits on age-associated lipid accumulation and hepatic steatosis, and the oral uptake of NR may be a promising strategy to prevent the progression of NAFLD.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7568
Author(s):  
Xue Han ◽  
Xiaogang Bao ◽  
Qi Lou ◽  
Xian Xie ◽  
Meng Zhang ◽  
...  

Background & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. Methods NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. Results NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Conclusion Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lucas Zangerolamo ◽  
Carina Solon ◽  
Gabriela M. Soares ◽  
Daiane F. Engel ◽  
Licio A. Velloso ◽  
...  

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia. While cognitive deficits remain the major manifestation of AD, metabolic and non-cognitive abnormalities, such as alterations in food intake, body weight and energy balance are also present, both in AD patients and animal models. In this sense, the tauroursodeoxycholic acid (TUDCA) has shown beneficial effects both in reducing the central and cognitive markers of AD, as well as in attenuating the metabolic disorders associated with it. We previously demonstrated that TUDCA improves glucose homeostasis and decreases the main AD neuromarkers in the streptozotocin-induced AD mouse model (Stz). Besides that, TUDCA-treated Stz mice showed lower body weight and adiposity. Here, we investigated the actions of TUDCA involved in the regulation of body weight and adiposity in Stz mice, since the effects of TUDCA in hypothalamic appetite control and energy homeostasis have not yet been explored in an AD mice model. The TUDCA-treated mice (Stz + TUDCA) displayed lower food intake, higher energy expenditure (EE) and respiratory quotient. In addition, we observed in the hypothalamus of the Stz + TUDCA mice reduced fluorescence and gene expression of inflammatory markers, as well as normalization of the orexigenic neuropeptides AgRP and NPY expression. Moreover, leptin-induced p-JAK2 and p-STAT3 signaling in the hypothalamus of Stz + TUDCA mice was improved, accompanied by reduced acute food intake after leptin stimulation. Taken together, we demonstrate that TUDCA treatment restores energy metabolism in Stz mice, a phenomenon that is associated with reduced food intake, increased EE and improved hypothalamic leptin signaling. These findings suggest treatment with TUDCA as a promising therapeutic intervention for the control of energy homeostasis in AD individuals.


Endocrinology ◽  
2021 ◽  
Author(s):  
Katharina Schnabl ◽  
Yongguo Li ◽  
Mueez U-Din ◽  
Martin Klingenspor

Abstract The obesity pandemic requires effective preventative and therapeutic intervention strategies. Successful and sustained obesity treatment is currently limited to bariatric surgery. Modulating the release of gut hormones is considered promising to mimic bariatric surgery with its beneficial effects on food intake, body weight and blood glucose levels. The gut peptide secretin was the first molecule to be termed a hormone; nevertheless, it only recently has been established as a legitimate anorexigenic peptide. In contrast to gut hormones that crosstalk with the brain either directly or by afferent neuronal projections, secretin mediates meal-associated brown fat thermogenesis to induce meal termination, thereby qualifying this physiological mechanism as an attractive, peripheral target for the treatment of obesity. In this perspective, it is of pivotal interest to deepen our yet superficial knowledge on the physiological roles of secretin as well as meal-associated thermogenesis in energy balance and body weight regulation. Of note, the emerging differences between meal-associated thermogenesis and cold-induced thermogenesis must be taken into account. In fact, there is no correlation between these two entities. In addition, the investigation of potential effects of secretin in hedonic-driven food intake, bariatric surgery as well as chronic treatment using suitable application strategies to overcome pharmacokinetic limitations will provide further insight into its potential to influence energy balance. The aim of this article is to review the facts on secretin’s metabolic effects, address prevailing gaps in our knowledge, and provide an overview on the opportunities and challenges of the therapeutic potential of secretin in body weight control.


1964 ◽  
Vol 206 (4) ◽  
pp. 762-764 ◽  
Author(s):  
Herbert Wohl ◽  
Clarence Merskey

Rats were divided into two groups such that mean weight and hemoglobin and hematocrit levels were not significantly different. One group (controls) was then fed a normal chow ad libitum. The other group was fed 6 g daily (30% of normal intake) for 2 weeks. The hemoglobin levels of rats fed the restricted diet rose 1.4–3.5 g/100 ml and hematocrit level rose 2–6%. At the end of 2 weeks total red cell mass (Cr51) was 5.5–6.0 ml in the underfed groups compared with 6.8 ml in the control group. Body weight fell proportionally more than did red cell mass, elevating the calculated red cell mass per unit body weight. Serum osmolality and K+ were not significantly different from control values, and there was a slightly higher serum Na+ and Cl– in the restricted diet group. It is concluded that restriction of food intake produced a relative polycythemia. At the end of 2 weeks of restriction an isosmotic reduction in plasma volume was present.


1961 ◽  
Vol 200 (6) ◽  
pp. 1277-1284 ◽  
Author(s):  
T. C. Smith ◽  
L. Will ◽  
J. Oleson ◽  
K. -F. Benitz ◽  
J. Perrine ◽  
...  

Response of transplanted and nontransplanted fat bodies to various hormones, tolbutamide, and hypoglycin A was compared by measuring the amount of lipids in the dissected fat bodies after 2 weeks treatment. Simultaneous measurements of food intake and body weight were made to serve as a basis for evaluating the effects on fat. Protamine zinc insulin produced an increase in lipid content of the testicular fat body, accompanied by elevation in food intake in three of five experiments; hydrocortisone acetate, triamcinolone or its 16,21-diacetate, or diethylstilbestrol brought about decreases in lipid with either no change or a decline in food intake; epinephrine·HCl or growth hormone elicited decreases in lipid without significantly influencing food intake or body weight. Generally, transplanted fat was more responsive to these agents than the undisturbed fat body. Both tolbutamide and hypoglycin A decreased lipids in the transplant without affecting those in untransplanted fat. Food intake, body weight, and blood glucose were not changed.


2021 ◽  
Vol 1 (1) ◽  
pp. 98-103
Author(s):  
Paola Quevedo da Costa ◽  
Mariana Parron Paim ◽  
Eduardo Echer dos Reis ◽  
Patrick Türck ◽  
Marli Camassola ◽  
...  

2019 ◽  
Vol 19 (6) ◽  
pp. 818-825 ◽  
Author(s):  
Julia Rodríguez-Castelán ◽  
Dafne Zepeda-Pérez ◽  
Maribel Méndez-Tepepa ◽  
Marlenne Castillo-Romano ◽  
Marlen Espíndola-Lozano ◽  
...  

Background: Hypothyroidism has been related to low-weight births, abortion and prematurity, which have been associated with changes in the content of glycogen and vascularization of the placenta. Since hypothyroidism can cause dyslipidemia, it may affect the lipid content in the uterus affecting the development of fetuses. Objective: To investigate the effect of hypothyroidism on the lipid levels in serum and uterus during pregnancy and their possible association with the size of fetuses. Methods: Adult female rabbits were grouped in control (n = 6) and hypothyroid (n = 6; treated with methimazole for 29 days before and 19 days after copulation). Food intake and body weight were daily registered. At gestational day 19 (GD19), dams were sacrificed under an overdose of anesthesia. Morphometric measures of fetuses were taken. Total cholesterol (TC), triglyceride (TAG), and glucose concentrations were quantified in blood, uterus and ovaries of dams. The expression of uterine 3β- hydroxysteroid dehydrogenase (3β-HSD) was quantified by Western blot. Results: Hypothyroidism reduced food intake and body weight of dams, as well as promoted low abdominal diameters of fetuses. It did not induce dyslipidemia and hyperglycemia at GD19 and did not modify the content of lipids in the ovary. However, it reduced the content of TAG and TC in the uterus, which was associated with uterine hyperplasia and an increased expression of 3β-HSD in the uterus. Conclusion: Hypothyroidism alters the lipid content in the uterus that might subsequently affect the energy production and lipid signaling important to fetal development.


Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 359 ◽  
Author(s):  
Mahli ◽  
Seitz ◽  
Freese ◽  
Frank ◽  
Weiskirchen ◽  
...  

Xanthohumol (XN), a prenylated chalcone from hops, has been reported to exhibit a variety of health-beneficial effects. However, poor bioavailability may limit its application in the prevention and therapy of diseases. The objective of this study was to determine whether a micellar solubilization of xanthohumol could enhance the bioavailability and biological efficacy of xanthohumol in a Western-type diet (WTD) induced model of obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). After 3 weeks feeding with WTD, XN was additionally applied per oral gavage as micellar solubilizate (s-XN) or native extract (n-XN) at a daily dose of 2.5 mg/kg body weight for a further 8 weeks. Control mice received vehicle only in addition to the WTD. WTD-induced body weight-gain and glucose intolerance were significantly inhibited by s-XN application. Furthermore, WTD-induced hepatic steatosis, pro-inflammatory gene expression (MCP-1 and CXCL1) and immune cell infiltration as well as activation of hepatic stellate cells (HSC) and expression of collagen alpha I were significantly reduced in the livers of s-XN-treated mice compared to WTD controls. In contrast, application of n-XN had no or only slight effects on the WTD-induced pathological effects. In line with this, plasma XN concentration ranged between 100–330 nmol/L in the s-XN group while XN was not detectable in the serum samples of n-XN-treated mice. In conclusion, micellar solubilization enhanced the bioavailability and beneficial effects of xanthohumol on different components of the metabolic syndrome including all pathological steps of NAFLD. Notably, this was achieved in a dose more than 10-fold lower than effective beneficial doses of native xanthohumol reported in previous in vivo studies.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Hyun-Jung Park ◽  
EunYee Jung ◽  
Insop Shim

Berberine (BBR), a natural plant product, has been shown to have antidiabetic, cholesterol-reducing effects. To investigate the action of BBR as appetite suppressants, two experimental protocols were performed. In the first experiment, the mice were fed either a normal-chow diet or a high-fat diet (HF). The mice received daily intraperitoneal injections of BBR (10 mg/kg or saline at 1 ml/kg) for 3 weeks. To determine the antiobesity effects of BBR, the food consumption, body weight, fat contents, serum leptin, and glucose level were investigated. In the second experiment, we set out to validate the effect of BBR on central neuropeptide Y (NPY) stimulated rats. Experiments were carried out in 24-hour fasted rats, and then food intake and glucose level were subsequently recorded for 1 hour. The experimental groups were subdivided into the intra-3rd ventricular microinjections of ACSF (artificial cerebrospinal fluid), neuropeptide Y (NPY; 100 nM), NPY+BBR (10 nM), and NPY+BBR (100 nM) group. And then the blood glucose level was examined. In the first experiment, treatment with BBR in the HF diet mice reduced food intake, body weight, fat contents, serum leptin, and glucose level. In the second experiment, the NPY-injected group increased food intake by 39.3%, and food intake was reduced in the BBR group by 47.5%, compared with the ACSF-injected group. Also, the serum glucose level in the NPY+BBR (100 nM) group was significantly lower than that in the NPY (100 nM) group. The results suggest that BBR improved lipid dysregulation in obesity by controlling the central obesity related pathway.


Sign in / Sign up

Export Citation Format

Share Document