GO:0010877 lipid transport involved in lipid storage: Lipid Storage Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0010877 describes the directed movement of lipids into cells as part of their accumulation and maintenance, a process central to energy homeostasis and membrane biogenesis.
• The term is a biological process that links extracellular lipid uptake, intracellular trafficking, and lipid droplet formation in tissues such as adipose, liver, and muscle.
• Key proteins include NPC1, NPC2, MIGA2, SLC7A10, and Arf1, which coordinate sterol egress, de novo lipogenesis, and lipid droplet dynamics.
• Defects in lipid transport and storage underlie Niemann-Pick disease type C, lipid storage myopathies, and metabolic syndrome features such as insulin resistance.
• CRISPR knockout, point-mutation, knock-in, and overexpression models are essential to dissect causal roles of candidate genes in lipid storage.
• EDITGENE provides end-to-end CRISPR services, including library screening and bioinformatics, to accelerate mechanistic and translational studies of lipid storage.
Description
GO:0010877, lipid transport involved in lipid storage, is a biological process defined as the directed movement of lipids into cells that is part of their accumulation and maintenance. This term captures the essential coupling between lipid uptake and storage, a process that is fundamental for energy balance, membrane synthesis, and cellular signaling. In multicellular organisms, the regulated transport of lipids into cells ensures that excess fatty acids and sterols are safely sequestered in lipid droplets, preventing lipotoxicity and maintaining metabolic flexibility. Research into GO:0010877 has revealed that this process is not a passive diffusion but an actively regulated network involving vesicular trafficking, lipid transfer proteins, and membrane contact sites. For example, the Niemann-Pick type C proteins NPC1 and NPC2 mediate the egress of cholesterol from lysosomes, a step required for subsequent lipid storage and homeostasis. Similarly, MIGA2 links mitochondria, the endoplasmic reticulum, and lipid droplets to promote de novo lipogenesis in adipocytes, directly connecting lipid transport to storage. Understanding GO:0010877 is critical because its dysregulation is associated with a spectrum of human diseases, including Niemann-Pick disease type C, lipid storage myopathies, and insulin resistance. Moreover, lipid-laden macrophages contribute to inflammation in atherosclerosis and other chronic conditions. Thus, dissecting the molecular players and regulatory mechanisms of lipid transport involved in lipid storage offers opportunities for therapeutic intervention and biomarker discovery.
lipid transport involved in lipid storage At A Glance
| GO ID | GO:0010877 |
|---|---|
| GO term | lipid transport involved in lipid storage |
| Ontology | biological_process |
| Synonym | None |
| Major function | Directed movement of lipids into cells for accumulation and maintenance |
| Related cellular components | Lipid droplets, endoplasmic reticulum, mitochondria-associated membranes, lysosomes |
| Key molecular players | NPC1, NPC2, MIGA2, SLC7A10, Arf1, leptin signaling components |
| Associated diseases | Niemann-Pick disease type C, lipid storage myopathies, insulin resistance, inflammation |
What Is GO:0010877?
GO:0010877, lipid transport involved in lipid storage, is defined by the Gene Ontology as the directed movement of lipids into cells that is part of their accumulation and maintenance. In other words, it encompasses all processes that move lipid molecules, such as fatty acids, cholesterol, and phospholipids, from the extracellular space or from intracellular sites of synthesis into storage compartments, primarily lipid droplets. This term is a child of lipid transport and is specifically tied to the context of lipid storage, distinguishing it from lipid transport for other purposes like membrane biogenesis or signaling. The process ensures that cells can store excess lipids in a safe, esterified form and mobilize them when energy is needed.
Why Is lipid transport involved in lipid storage Important in Cell Biology?
GO:0010877 is important because it sits at the intersection of energy metabolism, membrane biology, and disease. The ability of cells to transport and store lipids is essential for surviving periods of nutrient excess or scarcity. When this process fails, lipids accumulate in inappropriate tissues, leading to lipotoxicity, organ dysfunction, and metabolic disorders. For instance, mutations in NPC1 or NPC2 cause Niemann-Pick disease type C, a fatal neurodegenerative disorder characterized by impaired cholesterol transport and storage. Lipid storage myopathies represent another group of disorders where defective lipid transport and storage lead to muscle weakness and exercise intolerance. Furthermore, impaired adipocyte lipid storage is linked to insulin resistance and altered branched-chain amino acid metabolism. In the immune system, lipid scavenging by macrophages promotes inflammation, contributing to atherosclerosis and other chronic inflammatory diseases. Therefore, understanding GO:0010877 provides mechanistic insights into a wide range of pathologies and identifies potential targets for therapeutic intervention.
• Maintains energy homeostasis by storing excess lipids in lipid droplets for later oxidation.
• Prevents lipotoxicity by safely sequestering fatty acids and cholesterol in esterified forms.
• Supports membrane biogenesis and cellular growth by supplying lipids for new membranes.
• Dysregulation causes Niemann-Pick disease type C, a lysosomal storage disorder with neurodegeneration.
• Defects lead to lipid storage myopathies, characterized by muscle weakness and lipid accumulation in muscle fibers.
• Impaired adipocyte lipid storage is associated with insulin resistance and metabolic syndrome.
• Lipid-laden macrophages contribute to chronic inflammation in atherosclerosis and obesity.
• Hormonal signals such as leptin modulate lipid storage in reproductive tissues, affecting fertility.
• Crustacean hemolymph lipoproteins provide a comparative model for lipid transport and storage.
• Arf1 coordinates fatty acid metabolism with mitochondrial homeostasis, linking lipid storage to organelle function.
What Happens During lipid transport involved in lipid storage?
Lipid Uptake at the Plasma Membrane
In simple terms: Cells take in lipids from their surroundings through the cell membrane.
The first step in lipid transport involved in lipid storage is the uptake of lipids, such as fatty acids and cholesterol, from the extracellular environment. This can occur via protein-mediated transport, endocytosis, or scavenger receptor pathways. For example, lipid scavenging macrophages internalize modified lipoproteins, leading to lipid accumulation and inflammation. In adipocytes, fatty acid uptake is facilitated by transporters such as CD36 and FATP1, although the exact mechanisms are cell-type specific. The uptake step is tightly regulated by hormonal signals; leptin, for instance, increases lipid storage in Sertoli cells through specific signaling pathways. This initial transport ensures that lipids destined for storage enter the cell.
Intracellular Trafficking to Storage Organelles
In simple terms: Once inside, lipids are moved to storage sites like lipid droplets.
After entering the cell, lipids are trafficked to sites of esterification and storage. The endoplasmic reticulum (ER) is a major hub for lipid synthesis and lipid droplet formation. MIGA2, a protein that links mitochondria, the ER, and lipid droplets, promotes de novo lipogenesis in adipocytes, indicating that inter-organelle contact sites are critical for directing lipids to storage. Similarly, Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis, influencing how lipids are partitioned between storage and oxidation. Cholesterol egress from lysosomes, mediated by NPC1 and NPC2, is a prerequisite for its re-esterification and storage in lipid droplets. Thus, intracellular trafficking ensures that lipids reach the appropriate storage compartments.
Lipid Droplet Formation and Growth
In simple terms: Lipids are packaged into droplets inside the cell for long-term storage.
Lipid droplets are dynamic organelles that store neutral lipids, primarily triglycerides and cholesteryl esters. The formation of lipid droplets begins at the ER, where enzymes such as DGAT1 and DGAT2 catalyze the final step of triglyceride synthesis. The transport of lipids into these droplets is part of GO:0010877. Proteins like MIGA2 are localized at mitochondria-ER-lipid droplet contact sites and promote lipid storage in adipocytes. In Sertoli cells, leptin signaling increases lipid storage, likely by enhancing lipid droplet formation. The growth and maintenance of lipid droplets require continuous lipid transport, and defects in this process lead to ectopic lipid accumulation in non-adipose tissues.
Regulation by Hormones and Metabolic Signals
In simple terms: Hormones and nutrients tell cells when to store or use lipids.
Lipid transport involved in lipid storage is regulated by hormonal and nutritional signals. Leptin, an adipokine, increases lipid storage in Sertoli cells through signaling pathways that involve the JAK-STAT and PI3K-AKT cascades. Insulin promotes lipid storage in adipocytes by activating lipogenic enzymes and glucose uptake. In contrast, fasting and glucagon stimulate lipolysis, mobilizing stored lipids. The amino acid transporter SLC7A10 in adipocytes is linked to lipid storage and insulin resistance; its impairment leads to increased lipid accumulation and altered BCAA metabolism. These regulatory mechanisms ensure that lipid storage is matched to the organism's energy status.
Lipid Mobilization and Turnover
In simple terms: Stored lipids can be broken down and used when energy is needed.
Although GO:0010877 focuses on lipid transport into storage, the process is balanced by mobilization. Lipolysis releases fatty acids from lipid droplets for oxidation or export. The interplay between storage and mobilization is critical for metabolic flexibility. For example, Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis, influencing whether fatty acids are stored or burned. In lipid storage myopathies, impaired mobilization leads to excessive lipid accumulation in muscle. Thus, the transport of lipids into storage is dynamically regulated to meet cellular energy demands.
Key Genes Involved in GO:0010877 lipid transport involved in lipid storage
The following genes and proteins are central to lipid transport involved in lipid storage, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| NPC1 | Mediates cholesterol egress from lysosomes | Mutations cause Niemann-Pick disease type C; key for lysosomal lipid trafficking |
| NPC2 | Binds and transfers cholesterol within lysosomes | Defects lead to Niemann-Pick disease type C; involved in sterol transport |
| MIGA2 | Links mitochondria, ER, and lipid droplets; promotes de novo lipogenesis | Regulates adipocyte lipid storage; potential target for obesity |
| SLC7A10 | Amino acid transporter; influences lipid storage and insulin sensitivity | Impaired function promotes lipid storage and insulin resistance |
| Arf1 | Coordinates fatty acid metabolism and mitochondrial homeostasis | Links lipid storage to organelle function; potential therapeutic target |
| Leptin | Hormone that increases lipid storage in Sertoli cells | Regulates reproductive tissue lipid metabolism |
| CD36 | Fatty acid translocase; mediates fatty acid uptake | Involved in lipid scavenging by macrophages and adipocytes |
| DGAT1 | Diacylglycerol O-acyltransferase 1; synthesizes triglycerides | Enzyme for lipid droplet formation; target for metabolic diseases |
| DGAT2 | Diacylglycerol O-acyltransferase 2; synthesizes triglycerides | Critical for lipid droplet biogenesis and storage |
| PLIN1 | Perilipin 1; coats lipid droplets | Regulates lipolysis and lipid storage in adipocytes |
| PLIN2 | Perilipin 2; coats lipid droplets | Involved in lipid storage in non-adipose tissues |
| FATP1 | Fatty acid transport protein 1 | Facilitates fatty acid uptake for storage |
| ACSL1 | Acyl-CoA synthetase long-chain family member 1 | Activates fatty acids for esterification and storage |
| GPAT1 | Glycerol-3-phosphate acyltransferase 1 | First step in glycerolipid synthesis for storage |
| AGPAT2 | 1-acylglycerol-3-phosphate O-acyltransferase 2 | Mutations cause congenital generalized lipodystrophy |
| PAP1 | Phosphatidic acid phosphatase 1 | Generates diacylglycerol for triglyceride synthesis |
| CIDEC | Cell death-inducing DFFA-like effector c | Promotes lipid droplet enlargement and storage |
| LPL | Lipoprotein lipase | Hydrolyzes triglycerides for cellular uptake |
How Is lipid transport involved in lipid storage Regulated?
The process of lipid transport involved in lipid storage is regulated at multiple levels. Hormonal signals such as leptin and insulin promote lipid storage by activating lipogenic transcription factors like SREBP-1c and PPARγ. Nutrient availability, particularly glucose and fatty acids, directly influences the expression of transporters and enzymes involved in lipid uptake and esterification. At the post-translational level, proteins like Arf1 and MIGA2 are regulated by GTP binding and protein-protein interactions that control their localization to membrane contact sites. In adipocytes, SLC7A10 impairment leads to increased lipid storage and insulin resistance, suggesting a feedback loop between amino acid metabolism and lipid homeostasis. Additionally, inflammatory signals can alter lipid handling in macrophages, promoting foam cell formation. Thus, the regulation of GO:0010877 is complex and integrated with systemic metabolic status.
lipid transport involved in lipid storage and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| NPC1 | Niemann-Pick disease type C | NPC1 knockout mice or patient-derived iPSCs |
| NPC2 | Niemann-Pick disease type C | NPC2 knockout cell lines and mouse models |
| SLC7A10 | Insulin resistance, altered BCAA metabolism | Adipocyte-specific knockout or overexpression models |
| MIGA2 | Obesity, lipodystrophy | MIGA2 knockout adipocytes and mouse models |
| Arf1 | Metabolic disorders, mitochondrial dysfunction | Arf1 conditional knockout or point-mutation models |
Niemann-Pick Disease Type C
Niemann-Pick disease type C (NPC) is a lysosomal storage disorder caused by mutations in NPC1 or NPC2, leading to impaired cholesterol egress from lysosomes and subsequent accumulation of unesterified cholesterol and other lipids in various tissues, including the brain and liver. This defect in lipid transport involved in lipid storage results in progressive neurodegeneration, hepatosplenomegaly, and premature death. Research using NPC1 knockout models has been instrumental in elucidating the molecular basis of the disease and testing therapeutic strategies.
Lipid Storage Myopathies
Lipid storage myopathies are a group of inherited metabolic disorders characterized by abnormal accumulation of lipid droplets in muscle fibers, leading to muscle weakness and exercise intolerance. These conditions can result from defects in fatty acid oxidation, carnitine transport, or lipid droplet-associated proteins. The impaired transport of lipids into storage or their mobilization from storage contributes to the pathology. Diagnosis often involves muscle biopsy and genetic testing, and treatment may include dietary modifications and supplementation.
Insulin Resistance and Metabolic Syndrome
Impaired lipid storage in adipocytes is a hallmark of insulin resistance and metabolic syndrome. When adipocytes fail to store excess lipids, they accumulate in liver and muscle, causing lipotoxicity and interfering with insulin signaling. The amino acid transporter SLC7A10 has been implicated in this process; its downregulation in adipocytes promotes lipid storage and is associated with insulin resistance and altered BCAA metabolism. Thus, GO:0010877 is directly relevant to the pathogenesis of type 2 diabetes and related metabolic disorders.
Inflammation and Atherosclerosis
Lipid scavenging by macrophages is a key process in atherosclerosis. Macrophages take up modified lipoproteins and store the lipids as cholesteryl esters, becoming foam cells that contribute to plaque formation and inflammation. This lipid transport involved in lipid storage is mediated by scavenger receptors such as CD36 and SR-A. The resulting inflammatory response exacerbates vascular damage and promotes disease progression. Targeting these pathways is a major focus of cardiovascular research.
From lipid transport involved in lipid storage-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of NPC1 impair cholesterol storage? | NPC1 knockout cell lines (e.g., HeLa, CHO) and mouse models |
| How does MIGA2 regulate lipid droplet formation? | MIGA2 knockout and overexpression in 3T3-L1 adipocytes |
| What is the role of SLC7A10 in adipocyte lipid storage? | SLC7A10 knockout and knock-in in primary adipocytes |
| Does Arf1 coordinate fatty acid metabolism with mitochondria? | Arf1 point-mutation and knockout in hepatocytes |
| How does leptin signaling affect lipid storage in Sertoli cells? | Leptin receptor knockout and overexpression in Sertoli cell lines |
| Can CRISPR activation of lipid storage genes prevent lipotoxicity? | CRISPRa overexpression models in non-adipose cells |
How to Study the lipid transport involved in lipid storage Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screening | Loss-of-function phenotypes affecting lipid storage | Identify novel regulators of lipid transport |
| Lipidomics (LC-MS) | Quantification of lipid species | Profile changes in triglycerides and cholesteryl esters |
| Fluorescence microscopy | Lipid droplet number, size, and localization | Visualize lipid storage in cells and tissues |
| RNA-seq | Transcriptional changes | Identify pathways altered by gene knockout |
| Proteomics | Protein abundance and interactions | Discover lipid droplet-associated proteins |
| Western blot | Protein expression and phosphorylation | Validate knockout efficiency and signaling |
| qPCR | mRNA levels of target genes | Confirm gene expression changes |
| Seahorse assay | Mitochondrial respiration and fatty acid oxidation | Assess metabolic flux upon lipid storage manipulation |
CRISPR Screening for Lipid Storage Regulators
Genome-wide CRISPR knockout or activation screens can identify genes that regulate lipid transport involved in lipid storage. For example, a screen using lipid droplet staining as a readout can uncover novel regulators such as MIGA2 or SLC7A10. These screens are typically performed in cell lines like HepG2 or 3T3-L1 and validated with individual knockouts. The resulting hits provide candidates for further mechanistic studies and therapeutic targeting.
Lipidomics and Metabolomics
Mass spectrometry-based lipidomics allows comprehensive profiling of lipid species in cells and tissues. This method can quantify changes in triglycerides, cholesteryl esters, and phospholipids upon genetic manipulation of candidate genes. Metabolomics can also reveal alterations in amino acid metabolism, as seen with SLC7A10 impairment. These approaches are essential for understanding the biochemical consequences of altered lipid transport.
Imaging of Lipid Droplets and Trafficking
Fluorescence microscopy with lipid droplet dyes (e.g., BODIPY 493/503) and tagged proteins (e.g., GFP-NPC1) enables visualization of lipid storage and trafficking in live cells. Confocal and electron microscopy can reveal ultrastructural changes in organelles and membrane contact sites. Time-lapse imaging is particularly useful for studying the dynamics of lipid droplet formation and growth.
Transcriptomics and Proteomics
RNA sequencing (RNA-seq) and quantitative proteomics can identify global changes in gene and protein expression upon perturbation of lipid transport genes. For instance, knockout of SLC7A10 in adipocytes alters the expression of genes involved in BCAA metabolism and insulin signaling. Proteomic analysis of lipid droplet fractions can reveal novel proteins associated with storage organelles. These methods provide a systems-level view of the regulatory network.
How CRISPR Can Be Used to Study GO:0010877 lipid transport involved in lipid storage
Knockout
CRISPR knockout is used to completely ablate genes involved in lipid transport involved in lipid storage, such as NPC1, MIGA2, or SLC7A10, to study their loss-of-function phenotypes. For example, NPC1 knockout cells accumulate unesterified cholesterol in lysosomes, mimicking Niemann-Pick disease type C. Knockout of MIGA2 in adipocytes reduces de novo lipogenesis and lipid droplet formation. These models are essential for establishing causality and for drug screening.
Point Mutation
Point mutations can be introduced to model specific disease-associated variants or to dissect functional domains of proteins. For instance, mutations in NPC1 found in patients can be recapitulated in cell lines to study trafficking defects. Similarly, point mutations in Arf1 can reveal residues critical for its role in fatty acid metabolism. These models provide insights into structure-function relationships and personalized medicine.
Knock-in
Knock-in of reporter tags (e.g., GFP, HA) or disease alleles allows precise tracking of protein localization and function. Tagged NPC1 knock-in cells enable live-cell imaging of cholesterol transport. Knock-in of human disease mutations into mouse models can create more accurate representations of lipid storage disorders. This approach is valuable for studying protein dynamics and interactions in a physiological context.
Overexpression
CRISPR activation (CRISPRa) or cDNA overexpression can increase the levels of genes involved in lipid storage to study gain-of-function effects. Overexpression of MIGA2 in adipocytes enhances lipid droplet formation and storage. Overexpression of SLC7A10 may protect against lipid-induced insulin resistance. These models are useful for identifying protective mechanisms and potential therapeutic targets.
How EDITGENE Supports lipid transport involved in lipid storage Research
Researchers studying lipid transport involved in lipid storage-related genes often need to determine whether a candidate gene is causally involved in lipid accumulation, trafficking, or metabolic dysfunction. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such investigations, from gene knockout to precise point mutations and overexpression, along with library screening and bioinformatics support.
Contact EDITGENE today to design your custom CRISPR model for lipid transport involved in lipid storage research.
Frequently Asked Questions About lipid transport involved in lipid storage
What is GO:0010877?
GO:0010877 is a Gene Ontology biological process term defined as the directed movement of lipids into cells that is part of their accumulation and maintenance. It encompasses the transport steps that lead to lipid storage in organelles such as lipid droplets.
What genes are involved in lipid transport involved in lipid storage?
Key genes include NPC1, NPC2, MIGA2, SLC7A10, Arf1, and leptin, among others. These genes regulate various aspects of lipid uptake, trafficking, and storage.
How is lipid transport involved in lipid storage regulated?
It is regulated by hormonal signals (e.g., leptin, insulin), nutrient availability, and transcription factors such as SREBP-1c and PPARγ. Post-translational modifications and protein-protein interactions also control the localization and activity of transport proteins.
What diseases are associated with defects in lipid transport involved in lipid storage?
Defects are linked to Niemann-Pick disease type C, lipid storage myopathies, insulin resistance, metabolic syndrome, and atherosclerosis.
How can CRISPR be used to study lipid transport involved in lipid storage?
CRISPR knockout, point mutation, knock-in, and overexpression models allow researchers to dissect the causal roles of specific genes in lipid storage. For example, NPC1 knockout cells mimic Niemann-Pick disease type C, while MIGA2 overexpression enhances lipid droplet formation.
What methods are used to measure lipid storage?
Common methods include lipidomics, fluorescence microscopy with lipid droplet dyes, RNA-seq, proteomics, and metabolic flux assays. These techniques quantify lipid species, visualize storage organelles, and reveal molecular changes.
Which cell models are best for studying lipid transport involved in lipid storage?
Adipocytes (e.g., 3T3-L1), hepatocytes (e.g., HepG2), macrophages, and patient-derived fibroblasts are commonly used. The choice depends on the specific research question and tissue relevance.
What is the role of MIGA2 in lipid storage?
MIGA2 links mitochondria, the endoplasmic reticulum, and lipid droplets to promote de novo lipogenesis in adipocytes, thereby enhancing lipid storage.
How does SLC7A10 affect lipid storage?
Impaired SLC7A10 function in adipocytes promotes lipid storage and is associated with insulin resistance and altered branched-chain amino acid metabolism.
Can EDITGENE help with CRISPR screening for lipid storage genes?
Yes, EDITGENE provides custom CRISPR library screening services to identify novel regulators of lipid transport and storage, along with bioinformatics support for hit validation.
Conclusion
GO:0010877, lipid transport involved in lipid storage, is a fundamental biological process that ensures cellular energy balance and prevents lipotoxicity. Its dysregulation contributes to a range of diseases, from rare lysosomal storage disorders to common metabolic and inflammatory conditions. Continued research using advanced CRISPR models and multi-omics approaches will further unravel the molecular mechanisms and identify new therapeutic targets. EDITGENE stands ready to support these efforts with tailored CRISPR services and bioinformatics expertise.
References
- 1. Vanier MT. 2010. Niemann-Pick disease type C.. Orphanet J Rare Dis 5:16 PMID: 20525256
- 2. Enkler L et al.. 2023. Arf1 coordinates fatty acid metabolism and mitochondrial homeostasis.. Nat Cell Biol 25(8):1157-1172 PMID: 37400497
- 3. Freyre CAC et al.. 2019. MIGA2 Links Mitochondria, the ER, and Lipid Droplets and Promotes De Novo Lipogenesis in Adipocytes.. Mol Cell 76(5):811-825.e14 PMID: 31628041
- 4. Bruno C et al.. 2008. Lipid storage myopathies.. Curr Opin Neurol 21(5):601-6 PMID: 18769256
- 5. Hoeger U et al.. 2020. Crustacean Hemolymph Lipoproteins.. Subcell Biochem 94:35-62 PMID: 32189295
- 6. Vogel A et al.. 2022. Lipid scavenging macrophages and inflammation.. Biochim Biophys Acta Mol Cell Biol Lipids 1867(1):159066 PMID: 34626791
- 7. Dasso ME et al.. 2026. Leptin increases lipid storage in Sertoli cells: Signaling pathways and cellular mechanisms involved.. Biochimie 243:59-69 PMID: 41577290
- 8. Jersin RÅ et al.. 2023. Impaired Adipocyte SLC7A10 Promotes Lipid Storage in Association With Insulin Resistance and Altered BCAA Metabolism.. J Clin Endocrinol Metab 108(9):2217-2229 PMID: 36916878
