Endocrinology and Metabolism

Review Article

Diabetes, obesity and metabolism
The Emerging Importance of Mitochondria in White Adipocytes: Neither Last nor Least: Juan Cai, Fenfen Wang, Mengle Shao; Endocrinol Metab. 2023;38(5):493-503. Published online October 10, 2023; DOI: https://doi.org/10.3803/EnM.2023.1813

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The growing recognition of mitochondria’s crucial role in the regulation of white adipose tissue remodeling and energy balance underscores its significance. The marked metabolic diversity of mitochondria provides the molecular and cellular foundation for enabling adipose tissue plasticity in response to various metabolic cues. Effective control of mitochondrial function at the cellular level, not only in thermogenic brown and beige adipocytes but also in energy-storing white adipocytes, exerts a profound influence on adipose homeostasis. Furthermore, mitochondria play a pivotal role in intercellular communication within adipose tissue via production of metabolites with signaling properties. A more comprehensive understanding of mitochondrial regulation within white adipocytes will empower the development of targeted and efficacious strategies to enhance adipose function, leading to advancements in overall metabolic health.

Citations

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Aerobic glycolysis drives differentiation of unilocular adipocytes
Alice Maestri, Min Cai, Ruby Schipper, Julia Backman, Alana Vannay, Anneli Olsson, Ewa Ehrenborg, Roland Nilsson, Carolina E. Hagberg
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The Multiple Roles and Targeting Strategies of LonP1 in the Occurrence and Development of Cancer
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BioFactors.2026;[Epub] CrossRef
AAV-mediated FGF21 gene therapy promotes health span extension by whole-body tissue-specific adaptations
Veronica Jimenez, Victor Sacristan, Miquel Garcia, Claudia Jambrina, Estefania Casana, Sergio Muñoz, Laia Vilà, Ignasi Grass, Maria Luisa Jaén, Carles Roca, Xavier León, Sara Marcó, Maria Molas, Albert Ribera, Ivet Elias, Jordi Rodó, Tura Ferré, Fatima Bo
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Combining small extracellular vesicles with decellularized adipose tissue hydrogel for the construction of tissue-engineered adipose
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Unraveling the complexities of diet induced obesity and glucolipid dysfunction in metabolic syndrome
Babi Dutta, Aparna Tripathy, P. R. Archana, Shobha U. Kamath
Diabetology & Metabolic Syndrome.2025;[Epub] CrossRef
Protocol for differentiating murine 3T3-L1 and SVF-derived preadipocytes and isolating crude mitochondrial fractions
Churaibhon Wisessaowapak, Jeongmin Lee, Hyeonhui Kim, Seunghwan Son, Xue Feng, Lina Chang, Annie Hoang, Hetty Chen, Sarah Bedsted, Alan R. Saltiel
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DACRA induces profound weight loss, satiety control, and increased mitochondrial respiratory capacity in adipose tissue
Emilie A. Petersen, Ida Blom, Simone A. Melander, Mays Al-Rubai, Marina Vidotto, Louise T. Dalgaard, Morten A. Karsdal, Kim Henriksen, Steen Larsen, Anna T. Larsen
International Journal of Obesity.2024;[Epub] CrossRef
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Decreased mitochondrial‐related gene expression in adipose tissue after acute sprint exercise in humans: A pilot study
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Original Article

Diabetes, Obesity and Metabolism
Role of TRPV4 Channel in Human White Adipocytes Metabolic Activity: Julio C. Sánchez, Aníbal Valencia-Vásquez, Andrés M. García; Endocrinol Metab. 2021;36(5):997-1006. Published online October 14, 2021; DOI: https://doi.org/10.3803/EnM.2021.1167

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Background
Intracellular calcium (Ca²⁺) homeostasis plays an essential role in adipocyte metabolism and its alteration is associated with obesity and related disorders. Transient receptor potential vanilloid 4 (TRPV4) channels are an important Ca²⁺ pathway in adipocytes and their activity is regulated by metabolic mediators such as insulin. In this study, we evaluated the role of TRPV4 channels in metabolic activity and adipokine secretion in human white adipocytes.
Methods
Human white adipocytes were freshly cultured and the effects of the activation and inhibition of TRPV4 channels on lipolysis, glucose uptake, lactate production, and leptin and adiponectin secretion were evaluated.
Results
Under basal and isoproterenol-stimulated conditions, TRPV4 activation by GSK1016709A decreased lipolysis whereas HC067047, an antagonist, increased lipolysis. The activation of TRPV4 resulted in increased glucose uptake and lactate production under both basal conditions and insulin-stimulated conditions; in contrast HC067047 decreased both parameters. Leptin production was increased, and adiponectin production was diminished by TRPV4 activation and its inhibition had the opposite effect.
Conclusion
Our results suggested that TRPV4 channels are metabolic mediators involved in proadipogenic processes and glucose metabolism in adipocyte biology. TRPV4 channels could be a potential pharmacological target to treat metabolic disorders.

Citations

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Pengjiao Xi, Shuhui Ma, Derun Tian, Yanna Shen
International Journal of Molecular Sciences.2025; 26(5): 2296. CrossRef
Obesity, bone marrow adiposity, and leukemia: Time to act
Vijay Kumar, John H. Stewart
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TRP channels associated with macrophages as targets for the treatment of obese asthma
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Ion channels regulate energy homeostasis and the progression of metabolic disorders: Novel mechanisms and pharmacology of their modulators
Wenyi Wu, Jianan Zheng, Ru Wang, Yibing Wang
Biochemical Pharmacology.2023; 218: 115863. CrossRef
Potential lipolytic regulators derived from natural products as effective approaches to treat obesity
Xi-Ding Yang, Xing-Cheng Ge, Si-Yi Jiang, Yong-Yu Yang
Frontiers in Endocrinology.2022;[Epub] CrossRef
Adipokines: Deciphering the cardiovascular signature of adipose tissue
Joseph C. Galley, Shubhnita Singh, Wanessa M.C. Awata, Juliano V. Alves, Thiago Bruder-Nascimento
Biochemical Pharmacology.2022; 206: 115324. CrossRef

Namgok Lecture 2020

Diabetes, Obesity and Metabolism
Cellular and Intercellular Homeostasis in Adipose Tissue with Mitochondria-Specific Stress: Min Jeong Choi, Saet-Byel Jung, Joon Young Chang, Minho Shong; Endocrinol Metab. 2021;36(1):1-11. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.956

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Paracrine interactions are imperative for the maintenance of adipose tissue intercellular homeostasis, and intracellular organelle dysfunction results in local and systemic alterations in metabolic homeostasis. It is currently accepted that mitochondrial proteotoxic stress activates the mitochondrial unfolded protein response (UPR^mt) in vitro and in vivo. The induction of mitochondrial chaperones and proteases during the UPR^mt is a key cell-autonomous mechanism of mitochondrial quality control. The UPR^mt also affects systemic metabolism through the secretion of cell non-autonomous peptides and cytokines (hereafter, metabokines). Mitochondrial function in adipose tissue plays a pivotal role in whole-body metabolism and human diseases. Despite continuing interest in the role of the UPR^mt and quality control pathways of mitochondria in energy metabolism, studies on the roles of the UPR^mt and metabokines in white adipose tissue are relatively sparse. Here, we describe the role of the UPR^mt in adipose tissue, including adipocytes and resident macrophages, and the interactive roles of cell non-autonomous metabokines, particularly growth differentiation factor 15, in local adipose cellular homeostasis and systemic energy metabolism.

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The role and mechanism of UPRmt in adipocytes
Hao Liu, Jie Chen, Dan-Qi Qiu, Miao-Wei Jiang, Hao-Qi Chen, Li Li, Shu-Qin Chen
Adipocyte.2026;[Epub] CrossRef
From Microbial Switches to Metabolic Sensors: Rewiring the Gut–Brain Kynurenine Circuit
Masaru Tanaka, László Vécsei
Biomedicines.2025; 13(8): 2020. CrossRef
Imeglimin modulates mitochondria biology and facilitates mitokine secretion in 3T3-L1 adipocytes
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Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior
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Original Articles

Serum Preadipocyte Factor 1 Levels Are Not Associated with Bone Mineral Density among Healthy Postmenopausal Korean Women: Hoon Sung Choi, Sang-Wook Kim, Eun-Hee Cho; Endocrinol Metab. 2017;32(1):124-128. Published online February 28, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.124

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Background

Multipotent mesenchymal stem cells can differentiate into adipocytes or osteoblasts through closely regulated lineage-control processes. However, adipocyte precursor cells release preadipocyte factor 1 (Pref-1), which inhibits the differentiation of mesenchymal stem cells into mature adipocytes and osteoblasts. Previous studies have also reported an inverse association between Pref-1 levels and bone mineral density (BMD) among patients with anorexia nervosa.

Methods

In this retrospective study, we examined the correlations between Pref-1 levels and BMD among 124 healthy postmenopausal women (>50 years old). The patients had provided information regarding their clinical characteristics, and underwent blood testing and serum Pref-1 testing.

Results

The subjects' mean age was 59.9±7.1 years and the median time since menopause onset was 9.1 years. A history of osteoporotic fracture was identified in 23 subjects (19%). Serum Pref-1 levels were not significantly correlated with BMD values at the lumbar spine (R²=0.038, P=0.109), femur neck (R²=0.017, P=0.869), and total hip (R²=0.041, P=0.09), and multivariate analyses with adjustment for age and body mass index also did not detect any significant correlations. Subgroup analyses according to a history of fracture also did not detect significant associations between Pref-1 levels and BMD values.

Conclusion

In our study population, it does not appear that serum Pref-1 levels are significantly associated with BMD values and osteoporosis.

Citations

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Reexamining Fat: Exploring Diversity, Plasticity, Development, Functional Implication, and Therapeutic Options
Presley D. Dowker-Key, Praveen Kumar Jadi, Rawon Alfatlawi, Richard J. Giannone, Ahmed Bettaieb
International Journal of Molecular Sciences.2026; 27(4): 1925. CrossRef

Endocrine Research
The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes: Cheol Ryong Ku, Yoon Hee Cho, Zhen-Yu Hong, Ha Lee, Sue Ji Lee, Seung-soo Hong, Eun Jig Lee; Endocrinol Metab. 2016;31(2):328-335. Published online April 8, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.328

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Background

Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes.

Methods

For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments.

Results

RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group.

Conclusion

RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.

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Farideh Ghavidel, Seyed Isaac Hashemy, Mahdeyeh Aliari, Arezoo Rajabian, Masoud Homayouni Tabrizi, Stephen L. Atkin, Tannaz Jamialahmadi, Hossein Hosseini, Amirhossein Sahebkar
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Critical Reviews in Food Science and Nutrition.2025; 65(33): 8425. CrossRef
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Yida Wang, Hang Qi
Food Reviews International.2024; 40(1): 20. CrossRef
Resveratrol combats chronic diseases through enhancing mitochondrial quality
Weichu Tao, Hu Zhang, Xia Jiang, Ning Chen
Food Science and Human Wellness.2024; 13(2): 597. CrossRef
Polyphenol Compound 18a Modulates UCP1-Dependent Thermogenesis to Counteract Obesity
Xueping Wen, Yufei Song, Mei Zhang, Yiping Kang, Dandan Chen, Hui Ma, Fajun Nan, Yanan Duan, Jingya Li
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Detraining after short‐term exercise induces hyperphagia and obesity with fatty liver and brown adipose tissue whitening in young male OLETF rats
Takaya Oshima, Kaho Takaishi, Misuzu Nishihira, Son Tien Nguyen, Susumu Urakawa, Haruya Ohno, Naoto Fujita
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A comprehensive review of the health perspectives of resveratrol
Abdur Rauf, Muhammad Imran, Hafiz Ansar Rasul Suleria, Bashir Ahmad, Dennis G. Peters, Mohammad S. Mubarak
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Response: The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes (Endocrinol Metab2016;31:328-35, Cheol Ryong Ku et al.)
Cheol Ryong Ku, Eun Jig Lee
Endocrinology and Metabolism.2016; 31(3): 482. CrossRef
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Diabetes, Obesity and Metabolism
Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-α-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes: Seok-Woo Hong, Jinmi Lee, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2014;29(4):553-560. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.553

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Background

Tumor necrosis factor (TNF)-α and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated.

Methods

The key factors and mechanism of action of TNF-α and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 α (eIF2α) by Western blot and an immunofluorescence assay in 24-hour TNF-α-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation.

Results

Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-α-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-α and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2α, a component of the unfolded protein response signaling pathway, was observed in TNF-α or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-α-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2α.

Conclusion

These data indicated that AICAR-induced AMPK activation attenuates TNF-α-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2α activity is a novel mechanism of the anti-lipolytic effect of AICAR.

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Docosahexaenoic acid-enriched phospholipids and eicosapentaenoic acid-enriched phospholipids inhibit tumor necrosis factor-alpha-induced lipolysis in 3T3-L1 adipocytes by activating sirtuin 1 pathways
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Review Article

Diabetes, Obesity and Metabolism
Regulation of Adipocyte Differentiation via MicroRNAs: You Hwa Son, Sojeong Ka, A Young Kim, Jae Bum Kim; Endocrinol Metab. 2014;29(2):122-135. Published online June 26, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.2.122

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Adipocyte differentiation, termed adipogenesis, is a complicated process in which pluripotent mesenchymal stem cells differentiate into mature adipocytes. The process of adipocyte differentiation is tightly regulated by a number of transcription factors, hormones and signaling pathway molecules. Recent studies have demonstrated that microRNAs, which belong to small noncoding RNA species, are also involved in adipocyte differentiation. In vivo and in vitro studies have revealed that various microRNAs affect adipogenesis by targeting several adipogenic transcription factors and key signaling molecules. In this review, we will summarize the roles of microRNAs in adipogenesis and their target genes associated with each stage of adipocyte differentiation.

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Diba Dedacha Jilo, Belete Kuraz Abebe, Jianfang Wang, Juntao Guo, Haibing Liu, Qiu Liang, Anning Li, Linsen Zan
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Original Articles

Diabetes, Obesity and Metabolism
Association of Serum Adipocyte-Specific Fatty Acid Binding Protein with Fatty Liver Index as a Predictive Indicator of Nonalcoholic Fatty Liver Disease: Won Seon Jeon, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee; Endocrinol Metab. 2013;28(4):283-287. Published online December 12, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.4.283

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Background

Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein expressed in macrophages and adipocytes and it plays a role in insulin resistance and metabolic syndrome. Recently, the fatty liver index (FLI) was introduced as an indicator of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the relationship between baseline serum A-FABP levels and FLI after 4 years in apparently healthy subjects.

Methods

A total of 238 subjects without a past history of alcoholism or hepatitis were recruited from a medical check-up program. The NAFLD state was evaluated 4 years later in the same subjects using FLI. Fatty liver disease was diagnosed as diffusely increased echogenicity of the hepatic parenchyma compared to the kidneys, vascular blurring, and deep-echo attenuation. NAFLD was defined as subjects with fatty liver and no history of alcohol consumption (>20 g/day).

Results

Baseline serum A-FABP levels were significantly associated with FLI after adjustment for age and sex (P<0.001). The subjects with higher A-FABP levels had a higher mean FLI (P for trend=0.006). After adjusting for age and sex, serum A-FABP levels at baseline were shown to be significantly associated with FLI as a marker of development of NAFLD after 4 years (odds ratio, 2.68; 95% confidence interval, 1.24 to 5.80 for highest tertile vs. lowest tertile; P=0.012).

Conclusion

This study demonstrated that higher baseline serum A-FABP levels were associated with FLI as a predictive indicator of NAFLD after 4 years of follow-up in healthy Korean adults.

Citations

Citations to this article as recorded by

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Effect of 17-beta Estradiol on Adipocyte Lipin-1 Expression in OLETF Rat.: Eun Seok Kang, In Sook Kim, Seok Jin Ko, Chul Hoon Kim, Sung Wan Chun, Chul Woo Ahn, Bong Soo Cha, Hyun Chul Lee; Endocrinol Metab. 2010;25(3):199-205. Published online September 1, 2010; DOI: https://doi.org/10.3803/EnM.2010.25.3.199

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BACKGROUND
17 beta-estradiol is known to play an important role in glucose homeostasis. Lipin-1 is a nuclear protein that is essential in adipocyte differentiation and it is considered to play a role in ectopic fat deposition and the redistribution of fat. The aim of this study was to evaluate the effect of 17 beta-estradiol on the lipin-1 expression in the adipocytes of OLETF rats, which is an animal model of diabetes. METHODS: The OLETF rats were divided into 3 groups, 1) the sham-operation group (SHAM) 2) the castrated group (CAST) and 2) the castrated and estradiol treatment group (EST), and all the rats were at 6 weeks of age. LETO rats were used as a control group (LETO). 0.1 mg of estradiol valerate was injected subcutaneously every 4 weeks in the rats of the EST group. The visceral and subcutaneous tissues were isolated to evaluate the lipin-1 protein expression. The lipin-1 expression was measured in human visceral and subcutaneous preadipocytes. RESULTS: Less body weight gain was observed in the EST group compared with that of the SHAM group. In addition, improvement in the glucose tolerance was observed in the EST group. The lipin-1 expression in visceral fat was decreased in the SHAM and CAST groups, but it was but recovered in the EST group. The lipin-1 expression in the subcutaneous fat was decreased in the SHAM, CAST, and EST groups. CONCLUSION: Long term estradiol treatment in OLETF rats reduces the body weight gain and improves the glucose tolerance. Estradiol enhances the lipin-1 protein expression in the visceral adipocytes, but not in the subcutaneous adipocytes.

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Effect of 17-beta Estradiol on Adipocyte Lipin-1 Expression in OLETF Rat
Seong-Kyu Lee
Endocrinology and Metabolism.2010; 25(3): 177. CrossRef

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