Regulation of cholesterol storage in adipose tissue

Ángel, A.; Fárkas, J.

doi:10.1016/s0022-2275(20)36769-9

Cited by 61 publications

(7 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adipocytes are also known to be major vertebrate FC depot (48). Studies have also shown that the activation of lipolysis during fasting decreases the cellular level of TG in proportional to the cellular FC levels (59, 60), which supports our observation that fish fed HCD had increased plasma FC as well as FFA levels during fasting (Figure 4 C). We also observed increased FC in proportion to TG levels in fasted HCD fish (Figure 4 E).…”

Section: Discussionsupporting

confidence: 90%

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver triglycerides accumulation

Jin,

Kozan,

Anderson

et al. 2023

Preprint

View full text Add to dashboard Cite

Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. In this study, we provide an improved protocol to assay the impact of a high-cholesterol diet (HCD) on zebrafish lipid deposition and lipoprotein regulation. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LP) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae (8 days followed by a 1 day fast) and adult female fish (2 weeks, followed by 3 days of fasting) was also associated with a fatty liver phenotype that presented as severe hepatic steatosis. The HCD feeding paradigm doubled the levels of liver triacylglycerol (TG), which was striking because our HCD was only supplemented with cholesterol. The accumulated liver TG was unlikely due to increasedde novolipogenesis or inhibited β-oxidation since no differentially expressed genes in these pathways were found between the livers of fish fed the HCD versus control diets. However, fasted HCD fish had significantly increased lipogenesis genefasnin adipose tissue and higher free fatty acids (FFA) in plasma. This suggested that elevated dietary cholesterol resulted in lipid accumulation in adipocytes, which supplied more FFA during fasting, promoting hepatic steatosis. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease.

show abstract

Section: Discussionsupporting

confidence: 90%

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver triglycerides accumulation

Jin,

Kozan,

Anderson

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…The main function of white adipose tissue is to synthesize and store triglycerides and to release free fatty acids into the blood stream when needed. The size of adipocytes affects the weight of adipose tissue and is positively correlated to blood triglyceride level ( Angel and Farkas, 1974 , Kovanen et al., 1975 , Schreibman and Dell, 1975 , Krause and Hartman, 1976 ). Our current study was designed to test if the reduced serum total triglyceride levels observed in MCPIP1 knockout mice affects adipose tissue weight.…”

Section: Resultsmentioning

confidence: 99%

Systemic MCPIP1 deficiency in mice impairs lipid homeostasis

Moody

Yang

Sedinkin

et al. 2020

Current Research in Pharmacology and Drug Discovery

View full text Add to dashboard Cite

Atherosclerosis involves interactions between inflammation system and dyslipidemia. MCPIP1 (Monocyte Chemotactic Protein induced Protein-1) is induced by proinflammatory molecules and serves as a negative feedback loop in regulating inflammatory responses. Our current study was designed to test the role of MCPIP1 in maintaining lipid homeostasis, the latter a pivotal factor that contributes to the pathogenesis of atherosclerosis. We found that MCPIP1 knockout mice displayed a decrease in levels of serum HDL-cholesterol and total triglycerides but an increase in serum LDL/VLDL-cholesterol levels when compared to wild-type mice. Additionally, ApoA-1 expression was reduced but LPL expression was upregulated in plasma from MCPIP1 knockout mice. The livers from the MCPIP1 knockout mice revealed a decrease in hepatocyte number and an increase in collagen deposition when compared to wild-type mice. These findings suggest that MCPIP1 deficiency can induce liver fibrosis, alter the expression of lipoproteins, and affect transportation and metabolism of lipids, indicating that MCPIP1 is involved in maintaining lipid homeostasis, possibly via negatively regulating inflammatory responses.

show abstract

“…27 Thus, the regulation of whole-body cholesterol is dependent on the uptake and efflux of plasma lipoproteins, more than on its synthesis. 73 One example of this is the observation that thermogenic stimulation promotes HDL-C clearance and remodeling as well as increases macrophage to fecal reverse cholesterol transport in mice. [74][75][76][77] In humans, chronic treatment with mirabegron, a beta 3-adrenergic receptor agonist, increases BAT activity and elevates plasma HDL-C. 78 Increased cholesterol, a common finding during weight loss due to anorexia nervosa is thought to represent increased cholesterol release from adipose coupled to a defect in liver LDL uptake.…”

Section: Discussionmentioning

confidence: 99%

Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI–Mediated High-Density Lipoprotein Uptake

Thomas

Kaul

et al. 2021

ATVB

View full text Add to dashboard Cite

Objective: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)–mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. Approach and Results: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular protein-protein interactions, supporting SR-BI– mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI–mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI–mediated HDL-C uptake is unknown. Differentiated cells from Ldlr −/− / Pcpe2 −/− (Pcpe2 −/− ) and Ldlr −/− (control) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake. SR-BI–mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. Conclusions: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.

show abstract

Regulation of cholesterol storage in adipose tissue

Cited by 61 publications

References 22 publications

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver triglycerides accumulation

A high-cholesterol zebrafish diet promotes hypercholesterolemia and fasting-associated liver triglycerides accumulation

Systemic MCPIP1 deficiency in mice impairs lipid homeostasis

Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI–Mediated High-Density Lipoprotein Uptake

Contact Info

Product

Resources

About