Lipid metabolism is a critical component in preserving homeostasis and health, and lipids are significant chemicals involved in energy metabolism in living things. With the growing interest in lipid metabolism in recent years, an increasing number of studies have demonstrated the close relationship between abnormalities in lipid metabolism and the development of numerous human diseases, including cancer, cardiovascular, neurological, and endocrine system diseases. Thus, understanding how aberrant lipid metabolism contributes to the development of related diseases and how it works offers a theoretical foundation for treating and preventing related human diseases as well as new avenues for the targeted treatment of related diseases. Therefore, we discuss the processes of aberrant lipid metabolism in various human diseases in this review, including diseases of the cardiovascular system, neurodegenerative diseases, endocrine system diseases (such as obesity and type 2 diabetes mellitus), and other diseases including cancer.

BACKGROUND: Lipid metabolism disorders are associated with degeneration of multiple tissues and organs, but the mechanism of crosstalk between lipid metabolism disorder and intervertebral disc degeneration (IDD) has not been fully elucidated. In this study we aim to investigate the regulatory mechanism of abnormal signal of lipid metabolism disorder on intervertebral disc endplate chondrocyte (EPC) senescence and calcification.
METHODS: Human intervertebral disc cartilage endplate tissue, cell model and rat hyperlipemia model were performed in this study. Histology and immunohistochemistry were used to human EPC tissue detection. TMT-labelled quantitative proteomics was used to detect differential proteins, and MRI, micro-CT, safranin green staining and immunofluorescence were performed to observe the morphology and degeneration of rat tail intervertebral discs. Flow cytometry, senescence-associated β-galactosidase staining, alizarin red staining, alkaline phosphatase staining, DCFH-DA fluorescent probe, and western blot were performed to detect the expression of EPC cell senescence, senescence-associated secretory phenotype, calcification-related proteins and the activation of cell senescence-related signaling pathways.
RESULTS: Our study found that the highly expressed oxidized low-density lipoprotein (ox-LDL) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) in human degenerative EPC was associated with hyperlipidemia (HLP). TMT-labelled quantitative proteomics revealed enriched pathways such as cell cycle regulation, endochondral bone morphogenesis and inflammation. The rat model revealed that HLP could induce ox-LDL, LOX-1, senescence and calcification markers high expression in EPC. Moreover, we demonstrated that ox-LDL-induced EPCs senescence and calcification were dependent on the LOX-1 receptor, and the ROS/P38-MAPK/NF-κB signaling pathway was implicated in the regulation of senescence induced by ox-LDL/LOX-1 in cell model.
CONCLUSIONS: So our study revealed that ox-LDL/LOX-1-induced EPCs senescence and calcification through ROS/P38-MAPK/NF-κB signaling pathway, providing information on understanding the link between lipid metabolism disorders and IDD.

BACKGROUND: Hashimoto thyroiditis (HT), a common cause of hypothyroidism, has shown an increasing incidence in recent years, particularly among women. In addition to the common complications such as lipid metabolism disorders, patients with HT may also experience some serious complications, acute kidney injury and severe muscle damage for instance. This article explored the effectiveness of levothyroxine sodium tablets (L-T4) replacement therapy in severe complications of hypothyroidism, including treatment dosage, duration of complication recovery, and whether additional treatment is needed.
UNASSIGNED: We described a case of a 52-year-old woman with HT who exhibited kidney injury, muscle injury, and lipid metabolism disorders. The increased levels of serum creatinine, creatine kinase, cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and the decreased levels of estimated glomerular filtration rate were obviously observed. This patient was started on L-T4 (75 and 100 µg, alternate).
UNASSIGNED: Following a two-month treatment, the serum creatine kinase level decreased to within normal range. The estimated glomerular filtration rate level was restored, and the serum creatinine level was down-regulated, although slightly higher than the normal range. L-T4 partially reversed HT-induced the disorders of muscle, renal function, and lipid profile of this patient and remarkably alleviated her HT-related symptoms.

BACKGROUND: Older major depressive disorder (MDD) patients have more complex clinical symptoms and higher abnormal lipid metabolism (ALM) rates. This study aimed to compare clinical differences between those with and without ALM in a sample of older first-episode drug naïve (FEDN) patients.
METHODS: We recruited 266 older MDD patients. Socio-demographic variables, clinical data, and lipid parameters were obtained. The Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), and the positive subscale of the Positive and Negative Syndrome Scale (PANSS-P) were conducted to evaluate patients\' depression, anxiety and psychotic symptoms, respectively.
RESULTS: In this study, we found that the prevalence of comorbid ALM was 86.1% in older MDD patients. Compared with the non-abnormal lipid metabolism (NALM) group, the ALM group had a higher duration of illness, higher clinical global impression of severity scale (CGI-S) and HAMD scores, higher thyroid stimulating hormone (TSH) and glucose levels. Logistic regression analysis indicated that duration of illness (OR = 1.11, P = 0.023, 95%CI = 1.015-1.216) and CGI-S score (OR = 2.28, P = 0.014, 95%CI = 1.18-4.39) were associated with ALM in older MDD patients.
CONCLUSIONS: The importance of regular lipid assessment in older MDD patients needs to be taken into account.

Thyroid cancer (TC) is a neoplasm with an increasing incidence worldwide. Its etiology is complex and based on a multi-layered interplay of factors. Among these, disorders of lipid metabolism have emerged as an important area of investigation. Cancer cells are metabolically reprogrammed to promote their rapid growth, proliferation, and survival. This reprogramming is associated with significant changes at the level of lipids, mainly fatty acids (FA), as they play a critical role in maintaining cell structure, facilitating signaling pathways, and providing energy. These lipid-related changes help cancer cells meet the increased demands of continued growth and division while adapting to the tumor microenvironment. In this review, we examine lipid metabolism at different stages, including synthesis, transport, and oxidation, in the context of TC and the effects of obesity and hormones on TC development. Recent scientific efforts have revealed disturbances in lipid homeostasis that are specific to thyroid cancer, opening up potential avenues for early detection and targeted therapeutic interventions. Understanding the intricate metabolic pathways involved in FA metabolism may provide insights into potential interventions to prevent cancer progression and mitigate its effects on surrounding tissues.

Lipid metabolism disorders are a major cause of several chronic metabolic diseases which seriously affect public health. Salusin‑α, a vasoactive peptide, has been shown to attenuate lipid metabolism disorders, although its mechanism of action has not been reported. To investigate the effects and potential mechanisms of Salusin‑α on lipid metabolism, Salusin‑α was overexpressed or knocked down using lentiviral vectors. Hepatocyte steatosis was induced by free fatty acid (FFA) after lentiviral transfection into HepG2 cells. The degree of lipid accumulation was assessed using Oil Red O staining and by measuring several biochemical indices. Subsequently, bioinformatics was used to analyze the signaling pathways that may have been involved in lipid metabolism disorders. Finally, semi‑quantitative PCR and western blotting were used to verify the involvement of the liver kinase B1 (LKB1)/AMPK pathway. Compound C, an inhibitor of AMPK, was used to confirm this mechanism\'s involvement further. The results showed that Salusin‑α significantly attenuated lipid accumulation, inflammation and oxidative stress. In addition, Salusin‑α increased the levels of LKB1 and AMPK, which inhibited the expression of sterol regulatory element binding protein‑1c, fatty acid synthase and acetyl‑CoA carboxylase. The addition of Compound C abrogated the Salusin‑α‑mediated regulation of AMPK on downstream signaling molecules. In summary, overexpression of Salusin‑α activated the LKB1/AMPK pathway, which in turn inhibited lipid accumulation in HepG2 cells. This provides insights into the potential mechanism underlying the mechanism by which Salusin‑α ameliorates lipid metabolism disorders while identifying a potential therapeutic target.

The APOA1/C3/A4/A5 cluster is an essential component in regulating lipoprotein metabolism and maintaining plasma lipid homeostasis. A genome-wide association analysis and Mendelian randomization have revealed potential associations between genetic variants within this cluster and lipid metabolism disorders, including hyperlipidemia and cardiovascular events. An enhanced understanding of the complexity of gene regulation has led to growing recognition regarding the role of epigenetic variation in modulating APOA1/C3/A4/A5 gene expression. Intensive research into the epigenetic regulatory patterns of the APOA1/C3/A4/A5 cluster will help increase our understanding of the pathogenesis of lipid metabolism disorders and facilitate the development of new therapeutic approaches. This review discusses the biology of how the APOA1/C3/A4/A5 cluster affects circulating lipoproteins and the current progress in the epigenetic regulation of the APOA1/C3/A4/A5 cluster.

Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.

We present a young boy with a diagnosis of homozygous familial hypercholesterolemia who presented with statin and ezetimibe resistance. The patient received lipoprotein apheresis at 6 years of age. His low-density lipoprotein cholesterol levels significantly were reduced by adding lomitapide and evinacumab, and his carotid plaque started to regress.

OBJECTIVE: Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown.
METHODS: We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles.
RESULTS: The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.058, P = 0.011), total cholesterol (TC) (β = 0.100, P < 0.001), total triglycerides (TG) (β = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (β = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (β = 0.051, P = 0.049), apolipoprotein B (apoB) (β = 0.136, P < 0.001), apolipoprotein E (apoE) (β = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles.
CONCLUSIONS: We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA.
BACKGROUND: ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.