Apolipoprotein E in diet-induced obesity: a paradigm shift from conventional perception

Kypreos, Kyriakos E.; Karavia, Eleni A.; Constantinou, Caterina; Hatziri, Aikaterini; Kalogeropoulou, Christina; Xepapadaki, Eva; Zvintzou, Evangelia

doi:10.7555/jbr.32.20180007

Cited by 9 publications

(6 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interpretation of these traditional AD risk factors are complex. Several studies suggest a strong link between ApoE and overweight/obesity [ 82 ]. ApoE -/- mice accumulate less body fat content and possess smaller adipocytes compared to wild type C57BL/6 controls [ 83 ].…”

Section: Discussionmentioning

confidence: 99%

Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy

et al. 2021

View full text Add to dashboard Cite

Objective To test in mice with a double mutation of the ApoE gene (ApoE-/-) whether spinal cord injury (SCI) hastens the native trajectory of, and established component risks for, atherosclerotic disease (AD), and whether Salsalate anti-inflammatory pharmacotherapy attenuates the impact of SCI. Methods ApoE-/- mice were anesthetized and underwent a T9 laminectomy. Exposed spinal cords were given a contusion injury (70 k-dynes). Sham animals underwent all surgical procedures, excluding injury. Injured animals were randomized to 2 groups: SCI or SCI+Salsalate [120 mg/Kg/day i.p.]. Mice were serially sacrificed at 20-, 24-, and 28-weeks post-SCI, and body mass was recorded. At sacrifice, heart and aorta were harvested intact, fixed in 10% buffered formalin, cleaned and cut longitudinally for en face preparation. The aortic tree was stained with oil-red-O (ORO). AD lesion histomorphometry was calculated from the proportional area of ORO. Plasma total cholesterol, triglycerides and proatherogenic inflammatory cytokines (PAIC’s) were analyzed. Results AD lesion in the aortic arch progressively increased in ApoE-/-, significant at 24- and 28-weeks. AD in SCI is significantly greater at 24- and 28-weeks compared to time-controlled ApoE-/-. Salsalate treatment attenuates the SCI-induced increase at these time points. Body mass in all SCI groups are significantly reduced compared to time-controlled ApoE-/-. Cholesterol and triglycerides are significantly higher with SCI by 24- and 28-weeks, compared to ApoE-/-, and Salsalate reduces the SCI-induced effect on cholesterol. PAIC’s interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and chemokine (C-C motif) ligand 5 (CCL-5) are significantly greater with SCI compared to ApoE-/- at varying timepoints. Salsalate confers a marginal reducing effect on PAIC’s by 28-weeks compared to SCI. Regression models determine that each PAIC is a significant and positive predictor of lesion. (p’s <0.05). Conclusions SCI accelerates aortic AD and associated risk factors, and anti-inflammatory treatment may attenuate the impact of SCI on AD outcomes. PAIC’s IL-1β, IL-6, TNFα, MCP-1, and CCL-5 may be effective predictors of AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Another function of AGEs relevant to lipid metabolism is the inhibition of apolipoprotein E (ApoE) expression. ApoE, as a component of very low density lipoproteins (VLDLs), remnant lipoproteins, and high-density lipoproteins, contributes to lipoprotein internalization and degradation [ 47 , 48 ]. Using 3T3-L1 cells and mouse models, researchers observed that in hyperglycemic conditions, oxidative stress and the NF-κB pathway mediate ApoE abolishment.…”

Section: Influence Of the Rage Pathway On Adipose Tissue Activitymentioning

confidence: 99%

Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism

Gutowska

Czajkowski

Kuryłowicz

2023

IJMS

View full text Add to dashboard Cite

Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding of their membrane receptor (RAGE), AGEs affect numerous intracellular pathways and impair adipocyte differentiation, metabolism, and secretory activity. Therefore, inhibiting the production and accumulation of AGEs, as well as interfering with the metabolic pathways they activate, may be a promising therapeutic strategy for restoring normal adipose tissue function and, thus, combating obesity-related comorbidities. This narrative review summarizes data on the involvement of the RAGE pathway in adipose tissue dysfunction in obesity and the development of its metabolic complications. The paper begins with a brief review of AGE synthesis and the RAGE signaling pathway. The effect of the RAGE pathway on adipose tissue development and activity is then presented. Next, data from animal and human studies on the involvement of the RAGE pathway in obesity, diabetes, and cardiovascular diseases are summarized. Finally, therapeutic perspectives based on interference with the RAGE pathway are discussed.

show abstract

“…Briefly, APOE3 expressed in the brain inhibited oxidative phosphorylation in visceral WAT mitochondria, leading to increased body weight and obesity in response to a Western-type diet. In contrast, hepatic APOE3 expression (i.e., APOE3 presence only in the periphery) triggered increased thermogenesis in visceral WAT mitochondria, leading to a lean phenotype [ 39 ]. Yet, it is still unclear exactly how hepatically or cerebrally produced APOE affects WAT metabolism.…”

Section: High-density Lipoprotein and Adipose Tissue Metabolic Activitymentioning

confidence: 99%

“…Yet, it is still unclear exactly how hepatically or cerebrally produced APOE affects WAT metabolism. These findings constitute a major “paradigm shift” from the existing perception of Apoe when peripheral expression of APOE promotes obesity via receptor-mediated postprandial delivery of dietary lipids to WAT [ 39 ].…”

Section: High-density Lipoprotein and Adipose Tissue Metabolic Activitymentioning

confidence: 99%

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

Zvintzou,

Xepapadaki,

Skroubis

et al. 2023

Pharmaceuticals

View full text Add to dashboard Cite

High-density lipoprotein (HDL) is an enigmatic member of the plasma lipid and lipoprotein transport system, best known for its ability to promote the reverse cholesterol efflux and the unloading of excess cholesterol from peripheral tissues. More recently, data in experimental mice and humans suggest that HDL may play important novel roles in other physiological processes associated with various metabolic disorders. Important parameters in the HDL functions are its apolipoprotein and lipid content, further reinforcing the principle that HDL structure defines its functionality. Thus, based on current evidence, low levels of HDL-cholesterol (HDL-C) or dysfunctional HDL particles contribute to the development of metabolic diseases such as morbid obesity, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Interestingly, low levels of HDL-C and dysfunctional HDL particles are observed in patients with multiple myeloma and other types of cancer. Therefore, adjusting HDL-C levels within the optimal range and improving HDL particle functionality is expected to benefit such pathological conditions. The failure of previous clinical trials testing various HDL-C-raising pharmaceuticals does not preclude a significant role for HDL in the treatment of atherosclerosis and related metabolic disorders. Those trials were designed on the principle of “the more the better”, ignoring the U-shape relationship between HDL-C levels and morbidity and mortality. Thus, many of these pharmaceuticals should be retested in appropriately designed clinical trials. Novel gene-editing-based pharmaceuticals aiming at altering the apolipoprotein composition of HDL are expected to revolutionize the treatment strategies, improving the functionality of dysfunctional HDL.

show abstract

Apolipoprotein E in diet-induced obesity: a paradigm shift from conventional perception

Cited by 9 publications

References 65 publications

Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy

Cardiometabolic risks and atherosclerotic disease in ApoE knockout mice: Effect of spinal cord injury and Salsalate anti-inflammatory pharmacotherapy

Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism

High-Density Lipoprotein in Metabolic Disorders and Beyond: An Exciting New World Full of Challenges and Opportunities

Contact Info

Product

Resources

About