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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 15280

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Dr. Luis Varela

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Guest Editor

1. Achucarro Basque Center for Neuroscience, Science Park of the University of the Basque Country UPV/EHU, 48940 Leioa, Spain
2. IKERBASQUE, Basque Foundation for Science, Plaza Euskadi 5, 48009 Bilbao, Spain
Interests: hypothalamus; energy balance; mitochondria dynamics; astrocytes; lipid metabolism; AgRP neurons; POMC neurons; food intake

Special Issue Information

Dear Colleagues,

Lipids and fatty acids are key structural components of organisms; as such, they are involved in the maintenance of multiple physiological functions. They are important biomolecules, implicated in processes such as energy production through mitochondrial β-oxidation, structural integrity, and hormone regulation, among others.

Lipid metabolism refers to the synthesis and breakdown of tissue-specific lipidic species to fulfil the specific metabolic needs of a whole organism. The dysregulation of different lipid metabolism pathways has been implicated in the onset and development of pathologies associated with human disorders. Alterations of lipid metabolism in peripheral organs cause a wide range of metabolic disorders. In the CNS, lipid metabolism has been linked not only to pathologies associated with disrupted energy metabolism, but has also been shown to play crucial roles in the appearance and progression of different neurodegenerative diseases.

This Special Issue of the International Journal of Molecular Sciences, entitled “Lipid Metabolism in Human Diseases”, aims to publish original and review articles that increase our understanding of the role of lipid metabolism not only in metabolism-associated human disorders but also its implication in the progression of neurodegenerative diseases.

Dr. Luis Varela
Guest Editor

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Keywords

lipids
fatty acids
lipid metabolism
metabolic disorders
human diseases

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Published Papers (6 papers)

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Research

Jump to: Review

20 pages, 4449 KiB

Open AccessArticle

Fatty Acids and Their Lipogenic Enzymes in Anorexia Nervosa Clinical Subtypes

by Nhien Nguyen, D. Blake Woodside, Eileen Lam, Oswald Quehenberger, J. Bruce German and Pei-an Betty Shih

Int. J. Mol. Sci. 2024, 25(10), 5516; https://doi.org/10.3390/ijms25105516 - 18 May 2024

Viewed by 915

Abstract

Disordered eating behavior differs between the restricting subtype (AN-R) and the binging and purging subtype (AN-BP) of anorexia nervosa (AN). Yet, little is known about how these differences impact fatty acid (FA) dysregulation in AN. To address this question, we analyzed 26 FAs and 7 FA lipogenic enzymes (4 desaturases and 3 elongases) in 96 women: 25 AN-R, 25 AN-BP, and 46 healthy control women. Our goal was to assess subtype-specific patterns. Lauric acid was significantly higher in AN-BP than in AN-R at the fasting timepoint (p = 0.038) and displayed significantly different postprandial changes 2 h after eating. AN-R displayed significantly higher levels of n-3 alpha-linolenic acid, stearidonic acid, eicosapentaenoic acid (EPA), docosapentaenoic acid, and n-6 linoleic acid and gamma-linolenic acid compared to controls. AN-BP showed elevated EPA and saturated lauric acid compared to controls. Higher EPA was associated with elevated anxiety in AN-R (p = 0.035) but was linked to lower anxiety in AN-BP (p = 0.043). These findings suggest distinct disordered eating behaviors in AN subtypes contribute to lipid dysregulation and eating disorder comorbidities. A personalized dietary intervention may improve lipid dysregulation and enhance treatment effectiveness for AN. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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16 pages, 2847 KiB

Open AccessArticle

Gender-Specific Differences in Serum Sphingomyelin Species in Patients with Hepatitis C Virus Infection—Sphingomyelin Species Are Related to the Model of End-Stage Liver Disease (MELD) Score in Male Patients

by Georg Peschel, Kilian Weigand, Jonathan Grimm, Martina Müller, Sabrina Krautbauer, Marcus Höring, Gerhard Liebisch and Christa Buechler

Int. J. Mol. Sci. 2023, 24(9), 8402; https://doi.org/10.3390/ijms24098402 - 7 May 2023

Cited by 1 | Viewed by 1708

Abstract

Hepatitis C virus (HCV) replication depends on cellular sphingomyelin (SM), but serum SM composition in chronic HCV infection has been hardly analyzed. In this work, 18 SM species could be quantified in the serum of 178 patients with chronic HCV infection before therapy with direct-acting antivirals (DAAs) and 12 weeks later, when therapy was completed. Six SM species were higher in the serum of females than males before therapy and nine at the end of therapy; thus, sex-specific analysis was performed. Type 2 diabetes was associated with lower serum levels of SM 36:2;O2 and 38:2;O2 in men. Serum SM species did not correlate with the viral load in both sexes. Of note, three SM species were lower in males infected with HCV genotype 3 in comparison to genotype 1 infection. These SM species normalized after viral cure. SM 38:1;O2, 40:1;O2, 41:1;O2, and 42:1;O2 (and, thus, total SM levels) were higher in the serum of both sexes at the end of therapy. In males, SM 39:1;O2 was induced in addition, and higher levels of all of these SM species were already detected at 4 weeks after therapy has been started. Serum lipids are related to liver disease severity, and in females 15 serum SM species were low in patients with liver cirrhosis before initiation of and after treatment with DAAs. The serum SM species did not correlate with the model of end-stage liver disease (MELD) score in the cirrhosis and the non-cirrhosis subgroups in females. In HCV-infected male patients, nine SM species were lower in the serum of patients with cirrhosis before DAA treatment and eleven at the end of the study. Most of the SM species showed strong negative correlations with the MELD score in the male cirrhosis patients before DAA treatment and at the end of therapy. Associations of SM species with the MELD score were not detected in the non-cirrhosis male subgroup. In summary, the current analysis identified sex-specific differences in the serum levels of SM species in HCV infection, in liver cirrhosis, and during DAA therapy. Correlations of SM species with the MELD score in male but not in female patients indicate a much closer association between SM metabolism and liver function in male patients. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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15 pages, 2179 KiB

Open AccessArticle

MiR-19 Family Impairs Adipogenesis by the Downregulation of the PPARγ Transcriptional Network

by Paula Juiz-Valiña, Bárbara María Varela-Rodríguez, Elena Outeiriño-Blanco, María Jesús García-Brao, Enrique Mena, Fernando Cordido and Susana Sangiao-Alvarellos

Int. J. Mol. Sci. 2022, 23(24), 15792; https://doi.org/10.3390/ijms232415792 - 13 Dec 2022

Cited by 5 | Viewed by 1411

Abstract

microRNAs (miRNAs) are a class of small endogenous RNA that play pivotal roles in both the differentiation and function of adipocytes during the development of obesity. Despite this, only a few miRNA families have been identified as key players in adipogenesis. Here, we show the relevance of the miR-19 family, miR-19a and miR-19b, in lipid accumulation and the expansion of the adipose tissue in obesity. We observed that miR-19s were upregulated in the abdominal subcutaneous adipose tissue (aSAT) of human patients with morbid obesity, whereas after bariatric surgery, their expression was reduced. In vitro experiments identified miR-19a and b as crucial actors in adipogenesis and lipid accumulation. Overall, our results suggest a novel role of the miR-19 family in the regulatory networks underlying adipogenesis and, therefore, adipose tissue dysfunction. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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21 pages, 6339 KiB

Open AccessArticle

ATP-Binding Cassette Protein ABCC10 Deficiency Prevents Diet-Induced Obesity but Not Atherosclerosis in Mice

by Abeer Al Otaibi, Sindiyan Alshaikh Mubarak, Ali Al Qarni, Abbas Hawwari, Ahmed Bakillah and Jahangir Iqbal

Int. J. Mol. Sci. 2022, 23(22), 13813; https://doi.org/10.3390/ijms232213813 - 10 Nov 2022

Cited by 2 | Viewed by 1881

Abstract

Excess plasma lipid levels are a risk factor for various cardiometabolic disorders. Studies have shown that improving dyslipidemia lowers the progression of these disorders. In this study, we investigated the role of ATP-binding cassette transporter C10 (ABCC10) in regulating lipid metabolism. Our data indicate that deletion of the Abcc10 gene in male mice results in lower plasma and intestinal triglycerides by around 38% and 36%, respectively. Furthermore, deletion of ABCC10 ameliorates diet-induced obesity in mice and leads to a better response during insulin and glucose tolerance tests. Unexpectedly, ABCC10 deficiency does not affect triglyceride levels or atherosclerosis in ApoE-deficient mice. In addition, our studies demonstrate low oleate uptake by enterocytes (~25–30%) and less absorption (~37%) of triglycerides in the small intestine of ABCC10 knockout mice. Deletion of the Abcc10 gene also alters several lipid metabolism genes in the intestine, suggesting that ABCC10 regulates dietary fat absorption, which may contribute to diet-induced obesity in mice. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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15 pages, 1491 KiB

Open AccessArticle

Differential Effect of Dietary Supplementation with a Soybean Oil Enriched in Oleic Acid versus Linoleic Acid on Plasma Lipids and Atherosclerosis in LDLR-Deficient Mice

by Zhi-Hong Yang, Kimball Nill, Yuki Takechi-Haraya, Martin P. Playford, David Nguyen, Zu-Xi Yu, Milton Pryor, Jingrong Tang, Krishna Vamsi Rojulpote, Nehal N. Mehta, Han Wen and Alan T. Remaley

Int. J. Mol. Sci. 2022, 23(15), 8385; https://doi.org/10.3390/ijms23158385 - 29 Jul 2022

Cited by 20 | Viewed by 3576

Abstract

Both monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) play important roles in lipid metabolism, and diets enriched with either of these two fatty acids are associated with decreased cardiovascular risk. Conventional soybean oil (CSO), a common food ingredient, predominantly contains linoleic acid (LA; C18:2), a n-6 PUFA. Recently, a modified soybean oil (MSO) enriched in oleic acid (C18:1), a n-9 MUFA, has been developed, because of its improved chemical stability to oxidation. However, the effect of the different dietary soybean oils on cardiovascular disease remains unknown. To test whether diets rich in CSO versus MSO would attenuate atherosclerosis development, LDL receptor knock-out (LDLR-KO) mice were fed a Western diet enriched in saturated fatty acids (control), or a Western diet supplemented with 5% (w/w) LA-rich CSO or high-oleic MSO for 12 weeks. Both soybean oils contained a similar amount of linolenic acid (C18:3 n-3). The CSO diet decreased plasma lipid levels and the cholesterol content of VLDL and LDL by approximately 18% (p < 0.05), likely from increased hepatic levels of PUFA, which favorably regulated genes involved in cholesterol metabolism. The MSO diet, but not the CSO diet, suppressed atherosclerotic plaque size compared to the Western control diet (Control Western diet: 6.5 ± 0.9%; CSO diet: 6.4 ± 0.7%; MSO diet: 4.0 ± 0.5%) (p < 0.05), independent of plasma lipid level changes. The MSO diet also decreased the ratio of n-6/n-3 PUFA in the liver (Control Western diet: 4.5 ± 0.2; CSO diet: 6.1 ± 0.2; MSO diet: 2.9 ± 0.2) (p < 0.05), which correlated with favorable hepatic gene expression changes in lipid metabolism and markers of systemic inflammation. In conclusion, supplementation of the Western diet with MSO, but not CSO, reduced atherosclerosis development in LDLR-KO mice independent of changes in plasma lipids. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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Review

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23 pages, 2013 KiB

Open AccessReview

Current Understanding on the Role of Lipids in Macrophages and Associated Diseases

by Ida Florance and Seenivasan Ramasubbu

Int. J. Mol. Sci. 2023, 24(1), 589; https://doi.org/10.3390/ijms24010589 - 29 Dec 2022

Cited by 15 | Viewed by 4977

Abstract

Lipid metabolism is the major intracellular mechanism driving a variety of cellular functions such as energy storage, hormone regulation and cell division. Lipids, being a primary component of the cell membrane, play a pivotal role in the survival of macrophages. Lipids are crucial for a variety of macrophage functions including phagocytosis, energy balance and ageing. However, functions of lipids in macrophages vary based on the site the macrophages are residing at. Lipid-loaded macrophages have recently been emerging as a hallmark for several diseases. This review discusses the significance of lipids in adipose tissue macrophages, tumor-associated macrophages, microglia and peritoneal macrophages. Accumulation of macrophages with impaired lipid metabolism is often characteristically observed in several metabolic disorders. Stress signals differentially regulate lipid metabolism. While conditions such as hypoxia result in accumulation of lipids in macrophages, stress signals such as nutrient deprivation initiate lipolysis and clearance of lipids. Understanding the biology of lipid accumulation in macrophages requires the development of potentially active modulators of lipid metabolism. Full article

(This article belongs to the Special Issue Lipid Metabolism in Human Diseases)

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