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The Role of Lipids and Lipoproteins in Health

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Lipids".

Deadline for manuscript submissions: closed (25 October 2025) | Viewed by 10542

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Dr. Baohai Shao

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Department of Medicine, University of Washington, Seattle, WA, USA
Interests: mass spectrometry based proteomics; HDL, lipid metabolism and CVD risk in diabetes and kidney disease; oxidative stress and carbonyl stress in human diseases

Special Issue Information

Dear Colleagues,

Lipids are important for human health as they are carried and transported by lipoproteins to different tissues for normal cellular functions. However, blood lipid imbalance or dyslipidemia is harmful and can lead to various disorders. The most important lipoprotein-related diseases are heart disease and other cardiovascular diseases (CVD), which are the leading causes of death worldwide. There are different categories and types of lipoproteins, each playing a different role in cardiovascular diseases. For example, a key process in the pathogenesis of atherosclerosis, the major cause of heart attacks and peripheral vascular disease, is the accumulation of cholesterol-laden macrophages in the artery wall. Thus, one of the factors greatly increasing the risk of atherosclerotic cardiovascular disease is elevated levels of low-density lipoprotein (LDL), which delivers cholesterol to macrophages. In contrast, clinical, epidemiological, and animal studies have demonstrated a strong inverse relationship between high-density lipoprotein cholesterol (HDL-C) levels and CVD risk, strongly supporting the proposal that HDL is antiatherogenic. However, recent studies demonstrated that HDL functions (particularly cholesterol efflux capacity), HDL particle concentration, and HDL proteome are more important for the antiatherogenic properties of HDL than HDL-C levels.

In addition to cardiovascular diseases, lipoproteins play an important role in many other disorders, especially in diabetes and chronic kidney disease (CKD). Diabetic dyslipidemia is characterized by low HDL-C, elevated triglycerides, and elevated LDL-C, particularly small and dense LDL particles. These lipid changes represent a major link between diabetes and increased cardiovascular risk in diabetic patients. CKD patients also exhibit hypertriglyceridemia and low HDL-C levels; however, their LDL-C levels are mostly normal, as opposed to diabetic patients. Therefore, lower HDL levels in CKD patients might be a reason for the dramatically increased CVD risk and progression of CKD stages.

Despite advances in the study of lipoprotein metabolism, their functions, and their impact on disease over the past a few decades, the causal relationship between lipoproteins and different human diseases, as well as the underlying pathophysiological mechanisms remain unclear.

The purpose of this Special Issue is to publish new original discoveries and review articles to deepen our understanding of the role of different types of lipoproteins in the pathogenesis of various human diseases. It aims to identify innovative therapeutic strategies for the prevention or treatment of these diseases.

Dr. Baohai Shao
Guest Editor

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Keywords

lipids
lipoproteins
cholesterol
high-density lipoprotein (HDL)
atherosclerosis
cardiovascular disease (CVD)
chronic kidney disease
inflammation
low-density lipoprotein (LDL)
metabolic syndrome
diabetes
dyslipidemia

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Published Papers (6 papers)

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Research

13 pages, 512 KB

Open AccessArticle

Dysapolipoproteinaemia Influences the Relationship Between Very Low-Density Lipoprotein Cholesterol and Intra-Pancreatic Fat Deposition in Humans

by Yutong Liu, Loren Skudder-Hill, Juyeon Ko, Xiatiguli Shamaitijiang, Ivana R. Sequeira-Bisson and Maxim S. Petrov

Nutrients 2025, 17(23), 3718; https://doi.org/10.3390/nu17233718 - 27 Nov 2025

Viewed by 255

Abstract

Background: Apolipoprotein B (apo B), apolipoprotein C-II (apo C-II), and apolipoprotein C-III (apo C-III) play important roles in very low-density lipoprotein (VLDL) metabolism. Whether they influence the relationship between intra-pancreatic fat deposition (IPFD) and VLDL is unknown. The aim was to investigate whether the association between VLDL cholesterol (VLDL-C) and IPFD varies between individuals with and without dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III. Methods: Abdominal magnetic resonance imaging at 3T was performed to quantify IPFD. VLDL-C was measured using the Quantimetrix Lipoprint^® system, whereas apo B, apo C-II, and apo C-III levels were analysed using the MILLIPLEX^® (xMAP) assay. Dysapolipoproteinemia was defined as apolipoprotein levels above the upper quartile of the overall cohort. Univariable and multivariable linear regression analyses were performed, adjusting for age, sex, ethnicity, waist-to-hip ratio, high-density lipoprotein cholesterol, and insulin resistance. Results: A total of 32 individuals had dysapolipoproteinaemia, whereas 96 had normoapolipoproteinaemia. Among those with dysapolipoproteinaemia involving apo B, apo C-II, and apo C-III, VLDL-C levels were significantly and positively associated with IPFD. In the fully adjusted model, each unit increase in VLDL-C corresponded to a 0.82% (p = 0.011), 1.05% (p = 0.003), and 1.00% (p = 0.005) increase in IPFD, respectively. No significant association between VLDL-C and IPFD was observed in individuals with normoapolipoproteinaemia. Conclusions: Altered apolipoprotein profiles influence the association between VLDL-C and IPFD. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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13 pages, 960 KB

Open AccessArticle

Potential Effects of Nicotinamide on Serum HDL-Cholesterol Levels and Hepatic Oxidative Stress, ABCA1 Gene and Protein Expression in Rats Fed a High-Fat/Fructose Diet

by Jesús I. Serafín-Fabián, Armando Ramírez-Cruz, J. D. Villeda-González, Jaime Gómez-Zamudio, Adrián Hernández-Díazcouder, Clara Ortega-Camarillo, Eugenia Flores-Alfaro, Miguel Cruz and Miguel Vazquez-Moreno

Nutrients 2025, 17(21), 3458; https://doi.org/10.3390/nu17213458 - 1 Nov 2025

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Abstract

A hypercaloric diet is associated with oxidative stress and the dysfunction of ATP-Binding Cassette transporter A1 (ABCA1), a key element in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. Nicotinamide (NAM) presents antioxidant properties, which may contribute to maintaining lipid metabolism. Therefore, we aimed to evaluate the effect of NAM on HDL-cholesterol (HDL-C) level, oxidative stress markers, and the gene expression and protein levels of ABCA1 in Sprague-Dawley rats fed a hypercaloric diet. Forty male rats were divided into five groups: one group received a standard diet, and the remaining groups received a single high-fat, high-fructose diet (HFDF). Three of the HFDF groups received NAM treatment (5, 10, and 15 mM) in drinking water for 16 weeks (5 h/day). While HDL-C and oxidative stress were measured in serum samples, oxidative stress markers, and the gene expression and protein levels of ABCA1 were quantified in liver samples. The HDL-C level altered by the HFDF was improved by treatment with NAM. Furthermore, NAM reduces systemic lipid peroxidation levels and enhances the hepatic antioxidant response affected by the HFDF. In addition, NAM modulates the hepatic ABCA1 gene expression and protein level, altered by the HFDF. Our results suggest that NAM may modify the serum HDL-C level by an improvement of antioxidant response, and a possible modulation of the hepatic ABCA1 gene and protein expression. Further metabolic and molecular studies are needed to support the potential therapeutic role of NAM to prevent or treat lipid alterations promoted by a hypercaloric diet. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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17 pages, 23079 KB

Open AccessArticle

Intestinal Activation of LXRα Counteracts Metabolic-Associated Steatohepatitis Features in Mice

by Gessica Lioci, Fabio Gurrado, Nadia Panera, Marzia Bianchi, Cristiano De Stefanis, Valentina D’Oria, Nicolò Cicolani, Silvano Junior Santini, Laura Schiadà, Anna Alisi and Gianluca Svegliati-Baroni

Nutrients 2025, 17(8), 1349; https://doi.org/10.3390/nu17081349 - 15 Apr 2025

Viewed by 1263

Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem and the discovery of drugs is challenging. In this study, we aimed to investigate the effects of intestinal activation of the liver X receptor (LXR)α on MASH. Methods: An intestinal-specific LXRα activation model in mice was established and subjected to MASH development by combining a Western diet and carbon tetrachloride. Lipid metabolism, reverse cholesterol transport (RCT), steatosis, inflammation, and fibrosis were evaluated. In vitro models of steatosis and fibrosis were used to explore the role of scavenger receptor class B type 1 (SRB1). Results: We found that the intestinal activation of LXRα improved several MASLD features, including levels of triglycerides, RCT, steatosis, systemic and hepatic inflammatory profiles, and liver fibrosis. These effects were associated with increased high-density lipoprotein (HDL) levels and hepatic SRB1 expression. In vitro depletion of SRB1 hampered the beneficial effects of HDL on steatosis and fibrogenesis in liver cells by altering the activation of both peroxisome proliferator-activated receptors γ and small mothers against decapentaplegic homolog protein (SMAD)2/3 proteins. Conclusions: Our findings showed that the intestinal activation of LXRα and a parallel induction of hepatic SRB1 are protective against inflammation, steatosis, and advanced liver fibrosis in MASLD. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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12 pages, 414 KB

Open AccessArticle

Genetic and Anthropometric Interplay: How Waist-to-Hip Ratio Modulates LDL-c Levels in Mexican Population

by César Hernández-Guerrero, Erika Arenas, Jaime García-Mena, Edgar J. Mendivil, Omar Ramos-Lopez and Graciela Teruel

Nutrients 2024, 16(19), 3402; https://doi.org/10.3390/nu16193402 - 8 Oct 2024

Viewed by 2294

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Background/Objectives: Genetic factors contribute to the physiopathology of obesity and its comorbidities. This study aimed to investigate the association of the SNPs ABCA1 (rs9282541), ADIPOQ (rs2241766), FTO (rs9939609), GRB14 (rs10195252), and LEPR (rs1805134) with various clinical, anthropometric, and biochemical variables. Methods: The study included 396 Mexican mestizo individuals with obesity and 142 individuals with normal weight. Biochemical markers were evaluated from peripheral blood samples, and SNP genotyping was performed using PCR with TaqMan probes. A genetic risk score (GRS) was computed using an additive model. Results: No significant associations were found between the SNPs ABCA1, ADIPOQ, FTO, and LEPR with obesity. However, the T allele of the GRB14 SNP was significantly associated with obesity (χ² = 5.93, p = 0.01; OR = 1.52; 95% CI: 1.08–2.12). A multivariate linear regression model (adjusted R-squared: 0.1253; p < 0.001) predicting LDL-c levels among all participants (n = 538) identified significant (p < 0.05) beta coefficients for several anthropometric and biochemical variables, as well as for the GRS. Additionally, the interaction between the GRS and the waist-to-hip ratio (WHR) showed a negative beta coefficient (BC = −26.5307; p = 0.014). Participants with a WHR < 0.839 showed no effect of GRS on LDL-c concentration, while those with a WHR > 0.839 exhibited a greater effect of GRS (~9) at lower LDL-c concentrations (~50 mg/dL) and a lesser effect of GRS (~7) at higher LDL-c concentrations (~250 mg/dL). Conclusions: A significant interaction between genetics and WHR influences LDL-c in Mexicans, which may contribute to the prevention and clinical management of dyslipidemia and cardiovascular disease. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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17 pages, 1462 KB

Open AccessArticle

Usefulness of the ECORE-BF Scale to Determine Atherogenic Risk in 386,924 Spanish Workers

by Marta Marina Arroyo, Ignacio Ramírez Gallegos, Ángel Arturo López-González, María Teófila Vicente-Herrero, Daniela Vallejos, Tomás Sastre-Alzamora and José Ignacio Ramírez Manent

Nutrients 2024, 16(15), 2434; https://doi.org/10.3390/nu16152434 - 26 Jul 2024

Cited by 3 | Viewed by 1843

Abstract

Background: Cardiovascular diseases are the leading cause of death worldwide. Obesity and atherosclerosis are considered risk factors for this pathology. There are multiple methods to evaluate obesity, in the same way as there are different formulas to determine atherogenic risk. Since both pathologies are closely related, the objective of our work was to evaluate whether the ECORE-BF scale is capable of predicting atherogenic risk. Methods: Observational, descriptive, and cross-sectional study in which 386,924 workers from several autonomous communities in Spain participated. The association between the ECORE-BF scale and five atherogenic risk indices was evaluated. The relationship between variables was assessed using the chi-square test and Student’s t test in independent samples. Multivariate analysis was performed with the multinomial logistic regression test, calculating the odds ratio and 95% confidence intervals, with the Hosmer–Lemeshow goodness-of-fit test. ROC curves established the cut-off points for moderate and high vascular age and determined the Youden index. Results: The mean values of the ECORE-BF scale were higher in individuals with atherogenic dyslipidemia and the lipid triad, as well as in those with elevated values of the three atherogenic indices studied, with p <0.001 in all cases. As atherogenic risk increased across the five evaluated scales, the prevalence of obesity also significantly increased, with p <0.001 in all cases. In the ROC curve analysis, the AUCs for atherogenic dyslipidemia and the lipid triad were above 0.75, indicating a good association between these scales and the ECORE-BF. Although the Youden indices were not exceedingly high, they were around 0.5. Conclusions: There is a good association between atherogenic risk scales, atherogenic dyslipidemia, and lipid triad, and the ECORE-BF scale. The ECORE-BF scale can be a useful and quick tool to evaluate atherogenic risk in primary care and occupational medicine consultations without the need for blood tests. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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10 pages, 588 KB

Open AccessArticle

Triglyceride to HDL Cholesterol Ratio for the Identification of MASLD in Obesity: A Liver Biopsy-Based Case-Control Study

by José Ignacio Martínez-Montoro, María Antonia Martínez-Sánchez, Andrés Balaguer-Román, Virginia Esperanza Fernández-Ruiz, José Emilio Hernández-Barceló, Mercedes Ferrer-Gómez, María Dolores Frutos, María Ángeles Núñez-Sánchez, José Carlos Fernández-García and Bruno Ramos-Molina

Nutrients 2024, 16(9), 1310; https://doi.org/10.3390/nu16091310 - 27 Apr 2024

Cited by 8 | Viewed by 3168

Abstract

Associations between dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. Previous studies have shown that the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio may be a surrogate marker of MASLD, assessed by liver ultrasound. However, no studies have evaluated the utility of this ratio according to biopsy-proven MASLD and its stages. Therefore, our aim was to evaluate if the TG/HDL-C ratio allows for the identification of biopsy-proven MASLD in patients with obesity. We conducted a case-control study in 153 patients with obesity who underwent metabolic surgery and had a concomitant liver biopsy. Fifty-three patients were classified as no MASLD, 45 patients as metabolic dysfunction-associated steatotic liver—MASL, and 55 patients as metabolic dysfunction-associated steatohepatitis—MASH. A receiver operating characteristic (ROC) analysis was performed to assess the accuracy of the TG/HDL-C ratio to detect MASLD. We also compared the area under the curve (AUC) of the TG/HDL-C ratio, serum TG, and HDL-C. A higher TG/HDL-C ratio was observed among patients with MASLD, compared with patients without MASLD. No differences in the TG/HDL-C ratio were found between participants with MASL and MASH. The greatest AUC was observed for the TG/HDL-C ratio (AUC 0.747, p < 0.001) with a cut-off point of 3.7 for detecting MASLD (sensitivity = 70%; specificity = 74.5%). However, no statistically significant differences between the AUC of the TG/HDL-C ratio and TG or HDL-C were observed to detect MASLD. In conclusion, although an elevated TG/HDL-C ratio can be found in patients with MASLD, this marker did not improve the detection of MASLD in our study population, compared with either serum TG or HDL-C. Full article

(This article belongs to the Special Issue The Role of Lipids and Lipoproteins in Health)

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