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1.
Int J Mol Sci ; 23(18)2022 Sep 10.
Article in English | MEDLINE | ID: covidwho-2039867

ABSTRACT

Acute hepatopancreatic necrosis disease (AHPND), caused by a unique strain of Vibrio parahaemolyticus (Vp (AHPND)), has become the world's most severe debilitating disease in cultured shrimp. Thus far, the pathogenesis of AHPND remains largely unknow. Herein, in Litopenaeus vannamei, we found that a Vp (AHPND) infection significantly increased the expression of lipid droplets (LDs) protein LvPerilipin, as well as promoted the formation of LDs. In addition, the knockdown of LvPerilipin increased the shrimp survival rate in response to the Vp (AHPND) infection, and inhibited the proliferation of Vp (AHPND). Furthermore, we demonstrated that LvPerilipin depletion could increase the production of reactive oxygen species (ROS), which may be responsible for the decreased Vp (AHPND) proliferation. Taken together, our current data for the first time reveal that the shrimp lipid droplets protein Perilipin is involved in the pathogenesis of Vp (AHPND) via promoting LDs accumulation and decreasing ROS production.


Subject(s)
Penaeidae , Vibrio parahaemolyticus , Animals , Lipid Droplets , Perilipin-1 , Reactive Oxygen Species , Vibrio parahaemolyticus/physiology
2.
Int J Mol Sci ; 23(13)2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1934133

ABSTRACT

Casein kinase 2 (CK2) is a ubiquitously expressed serine/threonine kinase and is upregulated in human obesity. CX-4945 (Silmitasertib) is a CK2 inhibitor with anti-cancerous and anti-adipogenic activities. However, the anti-adipogenic and pro-lipolytic effects and the mode of action of CX-4945 in (pre)adipocytes remain elusive. Here, we explored the effects of CX-4945 on adipogenesis and lipolysis in differentiating and differentiated 3T3-L1 cells, a murine preadipocyte cell line. CX-4945 at 15 µM strongly reduced lipid droplet (LD) accumulation and triglyceride (TG) content in differentiating 3T3-L1 cells, indicating the drug's anti-adipogenic effect. Mechanistically, CX-4945 reduced the expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and perilipin A in differentiating 3T3-L1 cells. Strikingly, CX-4945 further increased the phosphorylation levels of cAMP-activated protein kinase (AMPK) and liver kinase B-1 (LKB-1) while decreasing the intracellular ATP content in differentiating 3T3-L1 cells. In differentiated 3T3-L1 cells, CX-4945 had abilities to stimulate glycerol release and elevate the phosphorylation levels of hormone-sensitive lipase (HSL), pointing to the drug's pro-lipolytic effect. In addition, CX-4945 induced the activation of extracellular signal-regulated kinase-1/2 (ERK-1/2), and PD98059, an inhibitor of ERK-1/2, attenuated the CX4945-induced glycerol release and HSL phosphorylation in differentiated 3T3-L1 cells, indicating the drug's ERK-1/2-dependent lipolysis. In summary, this investigation shows that CX-4945 has strong anti-adipogenic and pro-lipolytic effects on differentiating and differentiated 3T3-L1 cells, mediated by control of the expression and phosphorylation levels of CK2, C/EBP-α, PPAR-γ, FAS, ACC, perilipin A, AMPK, LKB-1, ERK-1/2, and HSL.


Subject(s)
Adipogenesis , Casein Kinase II , Naphthyridines , Phenazines , 3T3-L1 Cells , AMP-Activated Protein Kinases/metabolism , Animals , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Casein Kinase II/antagonists & inhibitors , Casein Kinase II/metabolism , Cell Differentiation/drug effects , Cyclic AMP-Dependent Protein Kinases/metabolism , Glycerol/pharmacology , Humans , Lipolysis/drug effects , Mice , Naphthyridines/pharmacology , PPAR gamma/metabolism , Perilipin-1/metabolism , Phenazines/pharmacology , Sterol Esterase/metabolism
3.
Nutrients ; 13(6)2021 Jun 11.
Article in English | MEDLINE | ID: covidwho-1448908

ABSTRACT

The role of post-therapeutic support after weight loss in obesity treatment is not fully understood. Therefore, weight maintenance after a successful weight loss intervention is not very common, especially in obese individuals. This randomized controlled study was conducted to explore the efficacy of following dietary and psychological support in a group of 36 obese individuals. Participants (22 women, 14 men aged 35.58 ± 9.85 years, BMI 35.04 ± 3.80 kg/m2) who completed a 12-month weight loss phase (balanced energy-restricted diet) were randomly allocated to receive 18-month support (SG) or no additional care (CG). The support phase included some elements of Ten Top Tips (TTT), cognitive behavioral therapy (CBT), motivational interviewing (MI) in combination with nutritional education and assessment of the level of physical activity. The primary outcome was the maintenance of anthropometric parameters at an 18-month follow-up. The secondary outcomes included evaluation of biochemical parameters and single nucleotide polymorphisms (SNPs) in genes connected with obesity. A comparison of SG vs. CG after a 30-month period of the study revealed significant differences in weight changes (-3.83 ± 6.09 vs. 2.48 ± 6.24 kg), Body Mass Index (-1.27 ± 2.02 vs. 0.72 ± 2.12 kg/m2), visceral adipose tissue (-0.58 ± 0.63 vs. 0.45 ± 0.74 L), and waist circumference (-4.83 ± 4.05 vs. 1.83 ± 5.97 cm). Analysis of SNPs (rs9939609 FTO, rs987237 TFAP2B, and rs894160 PLIN1) provided further insight into the potential modulating effect of certain genotypes on weight loss and maintenance and extended the knowledge of the potential benefits of personalized medicine. Post-therapeutical support in current clinical practice may increase the chances of long-term weight loss maintenance in obesity treatment even in patients with a genetic predisposition to excessive weight.


Subject(s)
Body Weight Maintenance , Counseling , Nutritionists , Obesity/therapy , Weight Loss , Weight Reduction Programs , Adult , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Body Composition , Cognitive Behavioral Therapy , Exercise , Female , Humans , Male , Motivational Interviewing , Perilipin-1/genetics , Polymorphism, Single Nucleotide , Transcription Factor AP-2/genetics
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