scholarly journals A New Strain of Christensenella minuta as a Potential Biotherapy for Obesity and Associated Metabolic Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 823
Author(s):  
Wilfrid Mazier ◽  
Katy Le Corf ◽  
Ccori Martinez ◽  
Héloïse Tudela ◽  
Déborah Kissi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Metabolic Diseases ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Hepatic Lipid Metabolism ◽  
Metabolic Markers ◽  
Shotgun Metagenomics ◽  
Hepatic Lipid ◽  
Diet Induced Obesity

Obesity is associated with gut microbiota dysbiosis, characterized by a high Firmicutes/Bacteroidetes ratio. Gut-dwelling bacteria of the Christensenellaceae family have been proposed to act as keystones of the human gut ecosystem and to prevent adipogenesis. The objectives of the present study were to demonstrate the antiobesity potential of a new strain of Christensenella minuta in preclinical models and explore related mechanisms of action. The antiobesity potential of C. minuta DSM33407 was assessed in a diet-induced obesity mouse model. Changes in hepatic lipid metabolism were explored using targeted transcriptomics. Effects on gut microbiota were further assessed in a humanized Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) model inoculated with obese fecal samples. Shotgun metagenomics was applied to study microbial community structures in both models. C. minuta DSM33407 protected from diet-induced obesity and regulated associated metabolic markers such as glycemia and leptin. It also regulated hepatic lipid metabolism through a strong inhibition of de novo lipogenesis and maintained gut epithelial integrity. In the humanized SHIME® model, these effects were associated with modulations of the intestinal microbiota characterized by a decreased Firmicutes/Bacteroidetes ratio. These data indicate that C. minuta DSM33407 is a convincing therapeutic candidate for the management of obesity and associated metabolic disorders.

scholarly journals Effect of Central Corticotropin-Releasing Factor on Hepatic Lipid Metabolism and Inflammation-Related Gene Expression in Rats

2021 ◽  
Vol 22 (8) ◽  
pp. 3940
Author(s):  
Yukiomi Nakade ◽  
Rena Kitano ◽  
Taeko Yamauchi ◽  
Satoshi Kimoto ◽  
Kazumasa Sakamoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
De Novo ◽  
Corticotropin Releasing Factor ◽  
De Novo Lipogenesis ◽  
Control Group ◽  
Mrna Levels ◽  
Related Gene ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

scholarly journals Fructose-enriched diet affects hepatic lipid metabolism in young male and female rats in different ways

2019 ◽  
Vol 71 (3) ◽  
pp. 417-424 ◽  
Author(s):  
Jelena Brkljacic ◽  
Natasa Velickovic ◽  
Ivana Elakovic ◽  
Ana Teofilovic ◽  
Danijela Vojnovic-Milutinovic ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Female Rats ◽  
Acid Oxidation ◽  
Hepatic Lipid Metabolism ◽  
Male And Female ◽  
Hepatic Lipid ◽  
Male And Female Rats ◽  
Dietary Fructose

An increase in fructose consumption coincides with a rising incidence of metabolic disorders. Dietary fructose has been shown to affect hepatic lipid metabolism in a way that may lead to lipid deposition in the liver. In this study, we tested the hypothesis that the effects of fructose overconsumption on hepatic lipid metabolism differ between sexes. To that end we examined the effects of a high-fructose diet on the expression of key enzymes and transcription factors involved in the regulation of fatty acid oxidation and de novo lipogenesis in the liver of 12-week-old male and female Wistar rats. Immediately after weaning, the rats were subjected to a standard diet and 10% fructose solution or drinking water for 9 weeks. The fructose-enriched diet induced hypertriglyceridemia and increased hepatic de novo lipogenesis in both sexes, without lipid deposition in the liver. At the same time, visceral adiposity was observed only in female rats, while in males the treatment stimulated hepatic fatty acid oxidation. The fructose-enriched diet induced sex-specific effects on hepatic lipid metabolism in young rats. These results imply that male and female rats employ different strategies to cope with dietary fructose-related energy overload and to avoid lipid accumulation in the liver. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. III41009]

scholarly journals ULK1 Regulates Hepatic Lipid Metabolism via Autophagy Independent Mechanisms

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A303-A303
Author(s):  
Young Do Koo ◽  
Romilia Tatiana Castillo ◽  
Antentor Othrell Hinton ◽  
Evan Dale Abel
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Chow Diet ◽  
Hepatic Lipid Metabolism ◽  
Critical Pathway ◽  
Hepatic Lipid ◽  
Normal Chow

Abstract Non-alcoholic steatohepatitis (NASH), a major complication of obesity, diabetes, and metabolic syndrome has emerged as a leading cause of chronic liver disease and a risk factor for hepatocellular carcinoma. Autophagy is a critical pathway for the degradation of intracellular components by lysosomes. Established functions for autophagy in hepatic lipid metabolism and insulin sensitivity suggest a mechanistic link between altered autophagy and NASH. However, the interactions between insulin sensitivity, NASH, and autophagy are incompletely understood. The Unc-51 Like Autophagy Activating Kinase 1 (ULK1) is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. In this study, we observed that ULK1 may directly regulate insulin signaling and lipid metabolism via mechanisms that might involve modulation of AKT dephosphorylation. Surprisingly, silencing ULK1 did not significantly alter autophagy in hepatocytes despite impairing insulin-stimulated activation of AKT. To further elucidate the autophagy-independent role of ULK1 in hepatic lipid metabolism and insulin action, ULK1 liver-specific knock-out mice were generated. L-ULK1 KO mice exhibited impaired glucose tolerance and insulin resistance on a normal chow diet or 60% high-fat diet (HFD). In young mice (4 weeks after birth), the expression of genes that regulate de novo lipogenesis, such as FAS, SCD1, and SREBP1-c were induced in livers of L-ULK1KO mice even prior to the development of insulin resistance and obesity. Hepatomegaly and lipid accumulation developed in L-ULK1KO on normal chow and was exacerbated relative to wild type mice on a HFD. Serum concentrations of insulin, triglyceride, cholesterol, AST and ALT were significantly increased. In contrast, L-ULK2 KO mice were phenotypically normal. To identify putative novel ULK1 targets, we conducted a phospho-proteomics screen in a ULK1 deficient hepatocyte cell line. We identified a relatively small number of novel proteins whose phosphorylation levels were reduced by ULK1 deficiency. The identification of these targets supports autophagy-independent mechanisms of action of ULK1. Recently, we confirmed that NCOA3, one of the targets regulates hepatic lipid metabolism by interacting directly with ULK1. These data suggest that ULK-1 may regulate cellular targets that regulate hepatic lipid metabolism and insulin sensitivity.

scholarly journals Hepatocyte-specific Sirt6 deficiency impairs ketogenesis

2018 ◽  
Vol 294 (5) ◽  
pp. 1579-1589 ◽  
Author(s):  
Lei Chen ◽  
Qinhui Liu ◽  
Qin Tang ◽  
Jiangying Kuang ◽  
Hong Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Hepatic Lipid Metabolism ◽  
Camp Response Element ◽  
Hepatic Lipid ◽  
Element Binding Protein ◽  
Regulate Lipid Metabolism

Sirt6 is an NADH (NAD+)-dependent deacetylase with a critical role in hepatic lipid metabolism. Ketogenesis is controlled by a signaling network of hepatic lipid metabolism. However, how Sirt6 functions in ketogenesis remains unclear. Here, we demonstrated that Sirt6 functions as a mediator of ketogenesis in response to a fasting and ketogenic diet (KD). The KD-fed hepatocyte-specific Sirt6 deficiency (HKO) mice exhibited impaired ketogenesis, which was due to enhanced Fsp27 (fat-specific induction of protein 27), a protein known to regulate lipid metabolism. In contrast, overexpression of Sirt6 in mouse primary hepatocytes promoted ketogenesis. Mechanistically, Sirt6 repressed Fsp27β expression by interacting with Crebh (cAMP response element–binding protein H) and preventing its recruitment to the Fsp27β gene promoter. The KD-fed HKO mice also showed exacerbated hepatic steatosis and inflammation. Finally, Fsp27 silencing rescued hypoketonemia and other metabolic phenotypes in KD-fed HKO mice. Our data suggest that the Sirt6–Crebh–Fsp27 axis is pivotal for hepatic lipid metabolism and inflammation. Sirt6 may be a pharmacological target to remedy metabolic diseases.

scholarly journals AMPK Activation Reduces Hepatic Lipid Content by Increasing Fat Oxidation In Vivo

2018 ◽  
Vol 19 (9) ◽  
pp. 2826 ◽  
Author(s):  
Marc Foretz ◽  
Patrick Even ◽  
Benoit Viollet
Keyword(s):  
Lipid Metabolism ◽  
De Novo ◽  
Fat Oxidation ◽  
De Novo Lipogenesis ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Hepatic Lipid ◽  
Adenoviral Delivery ◽  
Body Production

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver, achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

scholarly journals Probiotics L. plantarum and L. curvatus in Combination Alter Hepatic Lipid Metabolism and Suppress Diet-Induced Obesity

Obesity ◽  
2013 ◽  
Vol 21 (12) ◽  
pp. 2571-2578 ◽  
Author(s):  
Sae-Rom Yoo ◽  
Young-Jae Kim ◽  
Do-Young Park ◽  
Un-Ju Jung ◽  
Seon-Min Jeon ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Diet Induced Obesity

scholarly journals Herbal Formula HT048 Attenuates Diet-Induced Obesity by Improving Hepatic Lipid Metabolism and Insulin Resistance in Obese Rats

Molecules ◽  
2016 ◽  
Vol 21 (11) ◽  
pp. 1424 ◽  
Author(s):  
Yoon Lee ◽  
Bora Jin ◽  
Sung Lee ◽  
MiKyung Song ◽  
HyeonHui Bae ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Herbal Formula ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Diet Induced Obesity ◽  
Obese Rats

scholarly journals Effect of Gut Microbiota Modulation on Hepatic Lipid Metabolism in C57Bl/6 and ob/ob Mice

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Louise Tavares Garcia Pereira ◽  
Bruna Teles Soares Beserra ◽  
Daiane Fátima Engel ◽  
Gabriela Cristina Paula ◽  
Andreza Fabro Bem ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid

Hepatic lipid metabolism in adult rats using early weaning models: sex-related differences

2020 ◽  
Vol 11 (5) ◽  
pp. 499-508 ◽  
Author(s):  
Iala Milene Bertasso ◽  
Carla Bruna Pietrobon ◽  
Beatriz Souza da Silva ◽  
Rosiane Aparecida Miranda ◽  
Maria Lucia Bonfleur ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
De Novo ◽  
Liver Cholesterol ◽  
Control Group ◽  
Standard Diet ◽  
Early Weaning ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Normal Period ◽  
Liver Triglycerides

AbstractNon-pharmacological early weaning (NPEW) induces liver damage in male progeny at adulthood; however, pharmacological early weaning (PEW) does not cause this dysfunction. To elucidate this difference in liver dysfunction between these two models and determine the phenotype of female offspring, de novo lipogenesis, β-oxidation, very low-density lipoprotein (VLDL) export, and gluconeogenesis in both sexes were investigated in the adult Wistar rats that were weaned after a normal period of lactation (control group) or early weaned either by restriction of access to the dams’ teats (NPEW group) or by reduction of dams’ milk production with bromocriptine (PEW group). The offspring received standard diet from weaning to euthanasia (PN180). NPEW males had higher plasma triglycerides and TyG index, liver triglycerides, and cholesterol by de novo lipogenesis, which leads to intracellular lipids accumulation. As expected, hepatic morphology was preserved in PEW males, but they showed increased liver triglycerides. The only molecular difference between PEW and NPEW males was in acetyl-CoA carboxylase-1 (ACC-1) and stearoyl-CoA desaturase-1 (SCD-1), which were lower in PEW animals. Both early weaning (EW) females had no changes in liver cholesterol and triglyceride contents, and the hepatic cytoarchitecture was preserved. The expression of microsomal triglyceride transfer protein was increased in both the female EW groups, which could constitute a protective factor. The changes in hepatic lipid metabolism in EW offspring were less marked in females. EW impacted in the hepatic cytoarchitecture only in NPEW males, which showed higher ACC-1 and SCD-1 when compared to the PEW group. As these enzymes are lipogenic, it could explain a worsened liver function in NPEW males.

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