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Oxidative Medicine and Cellular... 2013Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these... (Review)
Review
Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these diseases. Nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Recent studies have proposed a close relationship between oxidative stress and energy metabolism-associated disease. The Nrf2 pathway, as a master regulator of cellular defense against oxidative stress, has emerged as a critical target of energy metabolism; however, its effects are controversial. This review examines the current state of research on the role of Nrf2 on energy metabolism, specifically with respect to its participation in adipocyte differentiation, obesity, and insulin resistance, and discusses the possibility of using Nrf2 as a therapeutic target in the clinic.
Topics: Adipocytes; Animals; Cell Differentiation; Humans; Insulin Resistance; NF-E2-Related Factor 2; Obesity
PubMed: 24194976
DOI: 10.1155/2013/184598 -
JCI Insight Mar 2021Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from...
Extracellular vesicles (EVs) are implicated in the crosstalk between adipocytes and other metabolic organs, and an altered biological cargo has been observed in EVs from human obese adipose tissue (AT). Yet, the role of adipocyte-derived EVs in pancreatic β cells remains to be determined. Here, we explored the effects of EVs released from adipocytes isolated from both rodents and humans and human AT explants on survival and function of pancreatic β cells and human pancreatic islets. EVs from healthy 3T3-L1 adipocytes increased survival and proliferation and promoted insulin secretion in INS-1E β cells and human pancreatic islets, both those untreated or exposed to cytokines or glucolipotoxicity, whereas EVs from inflamed adipocytes caused β cell death and dysfunction. Human lean adipocyte-derived EVs produced similar beneficial effects, whereas EVs from obese AT explants were harmful for human EndoC-βH3 β cells. We observed differential expression of miRNAs in EVs from healthy and inflamed adipocytes, as well as alteration in signaling pathways and expression of β cell genes, adipokines, and cytokines in recipient β cells. These in vitro results suggest that, depending on the physiopathological state of AT, adipocyte-derived EVs may influence β cell fate and function.
Topics: 3T3-L1 Cells; Adipocytes; Adipose Tissue; Adult; Animals; Extracellular Vesicles; Female; Humans; Islets of Langerhans; Male; Mice; Obesity
PubMed: 33539327
DOI: 10.1172/jci.insight.141962 -
Autophagy Dec 2023Macroautophagy/autophagy requires enormous membrane expansions during concerted actions of transient autophagic vesicles and lysosomes, yet the source of the membrane...
Macroautophagy/autophagy requires enormous membrane expansions during concerted actions of transient autophagic vesicles and lysosomes, yet the source of the membrane lipids is poorly understood. Recent work in adipocytes has now pinpointed the de novo lipogenesis pathway as the preferred source of fatty acids for phospholipid in autophagic membrane synthesis, as loss of FASN (fatty acid synthase) disrupts autophagic flux and lysosome function and . These data indicate fatty acid synthesis channels lipid for membrane expansions, whereas fatty acids from circulating lipoproteins provide for adipose lipid storage. Importantly, autophagy blockade upon loss of fatty acids promotes a strong thermogenic phenotype in adipocytes, another striking example whereby autophagy controls cell behavior.
Topics: Fatty Acids; Autophagy; Adipocytes; Lipogenesis; Phospholipids
PubMed: 37602798
DOI: 10.1080/15548627.2023.2246357 -
The Journal of Cell Biology Mar 2015Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine... (Review)
Review
Adipose tissue is a complex, multicellular organ that profoundly influences the function of nearly all other organ systems through its diverse metabolite and adipokine secretome. Adipocytes are the primary cell type of adipose tissue and play a key role in maintaining energy homeostasis. The efficiency with which adipose tissue responds to whole-body energetic demands reflects the ability of adipocytes to adapt to an altered nutrient environment, and has profound systemic implications. Deciphering adipocyte cell biology is an important component of understanding how the aberrant physiology of expanding adipose tissue contributes to the metabolic dysregulation associated with obesity.
Topics: Adipocytes; Adipose Tissue; Animals; Energy Metabolism; Humans; Obesity
PubMed: 25733711
DOI: 10.1083/jcb.201409063 -
Adipocyte 2018Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been... (Review)
Review
Obesity-induced adipose tissue inflammation is regulated by various immune cells for innate and adaptive immunity. Among adipose tissue immune cells, it has been proposed that invariant Natural Killer T (iNKT) cells play crucial roles in anti-inflammatory responses in obesity. iNKT cells recognize 'lipid' antigens loaded on CD1d of antigen presenting cells and modulate immune responses by secreting Th1 or Th2 type cytokines depending on species of lipid antigens, antigen presenting cell types, and environmental cytokine milieu. However, the regulatory mechanisms of antigen presenting cells for adipose iNKT cell stimulation have not been clearly elucidated. Recently, we have reported that CD1d expressing adipocytes could act as an antigen presenting cell for adipose iNKT cells by characterization of adipocyte-specific CD1d knockout (CD1d) mice. Upon high-fat diet (HFD) feeding, CD1d mice aggravated adipose tissue inflammation and insulin resistance compared with CD1d mice. In this commentary, we provide the additional data of adipocyte CD1d-dependent regulation of adipose iNKT cell responses as well as systemic insulin sensitivity. In addition, we discuss how the interaction between adipocytes and iNKT cells would be regulated with the progression of obesity.
Topics: Adipocytes; Animals; Antigens, CD1d; Humans; Inflammation; Insulin Resistance; Mice; Natural Killer T-Cells; Obesity
PubMed: 29509047
DOI: 10.1080/21623945.2018.1440928 -
Trends in Endocrinology and Metabolism:... Jan 2016Dermal white adipose tissue (dWAT) has received little appreciation in the past as a distinct entity from the better recognized subcutaneous white adipose tissue (sWAT).... (Review)
Review
Dermal white adipose tissue (dWAT) has received little appreciation in the past as a distinct entity from the better recognized subcutaneous white adipose tissue (sWAT). However, recent work has established dWAT as an important contributor to a multitude of processes, including immune response, wound healing and scarring, hair follicle (HF) growth, and thermoregulation. Unique metabolic contributions have also been attributed to dWAT, at least in part due to its thermic insulation properties and response to cold exposure. Dermal adipocytes can also undergo an adipocyte-myofibroblast transition (AMT), a process that is suspected to have an important role in several pathophysiological processes within the skin. Here, we discuss emerging concepts regarding dWAT physiology and its significance to a variety of cellular processes.
Topics: Adipocytes; Adipose Tissue, White; Animals; Hair Follicle; Humans; Wound Healing
PubMed: 26643658
DOI: 10.1016/j.tem.2015.11.002 -
Cytometry. Part a : the Journal of the... Feb 2018Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell...
Adipocyte infiltration in the bone marrow follows chemotherapy or irradiation. Previous studies indicate that bone marrow fat cells inhibit hematopoietic stem cell function. Recently, Zhou et al. (2017) using state-of-the-art techniques, including sophisticated Cre/loxP technologies, confocal microscopy, in vivo lineage-tracing, flow cytometry, and bone marrow transplantation, reveal that adipocytes promote hematopoietic recovery after irradiation. This study challenges the current view of adipocytes as negative regulators of the hematopoietic stem cells niche, and reopens the discussion about adipocytes' roles in the bone marrow. Strikingly, genetic deletion of stem cell factor specifically from adipocytes leads to deficiency in hematopoietic stem cells, and reduces animal survival after myeloablation, The emerging knowledge from this research will be important for the treatment of multiple hematologic disorders. © 2017 International Society for Advancement of Cytometry.
Topics: Adipocytes; Animals; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Hematopoietic Stem Cells; Humans
PubMed: 29236351
DOI: 10.1002/cyto.a.23301 -
Journal of Biomedical Science Dec 2018Obesity is one of the most invaliding and preventable diseases in the United States. Growing evidence suggests that there are sex differences in obesity in human and... (Review)
Review
Obesity is one of the most invaliding and preventable diseases in the United States. Growing evidence suggests that there are sex differences in obesity in human and experimental animals. However, the specific mechanisms of this disease are unknown. Consequently, there is any particular treatment according to the sex/gender at this time. During the last decade, we observe a rise in the study of adipocyte and the possible mechanisms involved in the different roles of the fat. Furthermore, the effect of sex steroids on the adipocyte is one of the fields that need elucidation. Supporting evidence suggests that sex steroids play an essential role not only in the fat distribution, but also, in its metabolism, proliferation, and function. Thus, using in vitro and in vivo studies will contribute to our fight against this critical health public problem encompassing both sexes. In the present review, we discuss some of the recent advances in the adipocytes and the effect of the sex steroids on the adipose tissue. Also, we propose a new alternative to study the role of sex steroids on adipocyte biology through human adipose-derived stem cells.
Topics: Adipocytes; Animals; Female; Gonadal Steroid Hormones; Humans; Male; Mice; Rats; Sex Factors
PubMed: 30509250
DOI: 10.1186/s12929-018-0488-3 -
Biochimica Et Biophysica Acta.... Jun 2021KAT8 is a lysine acetyltransferase (KAT) that plays a role in a variety of cellular functions ranging from DNA damage repair to apoptosis. The role of KAT8 in adipocyte...
KAT8 is a lysine acetyltransferase (KAT) that plays a role in a variety of cellular functions ranging from DNA damage repair to apoptosis. The role of KAT8 in adipocyte development and function has not been studied. Notably, a large genome-wide association study identified KAT8 as part of a novel locus that significantly contributed to body mass index and other metabolic phenotypes. Hence, we examined the expression and regulation of KAT8 during adipocyte development. KAT8 mRNA and protein levels were examined over a time course of adipocyte development, and KAT8 was found to be present in both the cytosol and nucleus of 3T3-L1 adipocytes. Although KAT8 expression was not highly regulated by adipogenesis, its expression was required for the adipogenesis of 3T3-L1 cells. Loss of KAT8 expression in preadipocytes inhibited their ability to differentiate as judged by both lipid accumulation and adipocyte marker gene expression. However, if KAT8 was knocked down after clonal expansion, its absence did not inhibit adipocyte differentiation. Also, loss of KAT8 in adipocytes did not impact lipid accumulation or the expression of adiponectin or other fat markers. Although our data demonstrate that KAT8 is required for adipocyte differentiation, further studies are necessary to determine the functions and regulation of KAT8 in adipose tissue.
Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Cell Differentiation; Histone Acetyltransferases; In Vitro Techniques; Mice
PubMed: 33617987
DOI: 10.1016/j.bbadis.2021.166103 -
International Journal of Obesity (2005) Aug 2017White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with...
OBJECTIVES
White adipose tissue (WAT) expands through hypertrophy (increased adipocyte size) and/or hyperplasia (increased adipocyte number). Hypertrophy has been associated with insulin resistance and dyslipidemia independently of body composition and fat distribution. In contrast, hyperplasia protects against metabolic alterations. Proanthocyanidins, which are the most abundant flavonoids in the human diet, improve metabolic disturbances associated with diet-induced obesity without reducing body weight or adiposity. The aim of this study was to determine whether grape seed proanthocyanidin extract (GSPE) can modulate WAT expandability. Because GSPE also contains gallic acid, we also studied the capacity of gallic acid to remodel WAT.
DESIGN
Male Wistar rats were fed a standard chow diet (n=6) or a cafeteria diet (CAF) for 11 weeks. After 8 weeks, the CAF-fed animals were supplemented with 25 mg GSPE/kg body weight (n=6), 7 mg gallic acid/kg body weight (n=6) or the vehicle (n=6) for 3 weeks. Histological analyses were performed in the retroperitoneal (rWAT) and inguinal (iWAT) WAT to determine adipocyte size and number. Specific markers for adipogenesis and WAT functionality were analysed in rWAT using quantitative RT-PCR.
RESULTS
GSPE or gallic acid supplementation did not reduce weight gain or reverse and adiposity. However, GSPE reduced adipocyte size significantly in rWAT and moderately in iWAT and tripled the adipocyte number in rWAT. Gallic acid slightly reduced adipocyte size in rWAT and iWAT and doubled the adipocyte number in both WATs. In accordance with this adipogenic activity, Pref-1 and PPARγ tended to be overexpressed in rWAT of rats supplemented with GSPE. Moreover, GSPE supplementation increased Plin1 and Fabp4 expression and restored adiponectin expression completely, indicating a better functionality of visceral WAT.
CONCLUSIONS
GSPE supplementation has anti-hypertrophic and hyperplasic activities in rats with established obesity, mainly in visceral WAT inducing a healthier expansion of WAT to match the surplus energy provided by the cafeteria diet.
Topics: Adipocytes; Adiposity; Animals; Antioxidants; Disease Models, Animal; Fatty Acid-Binding Proteins; Gallic Acid; Gene Expression Regulation; Grape Seed Extract; Lipid Metabolism; Male; Obesity; Perilipin-1; Proanthocyanidins; Rats; Rats, Wistar
PubMed: 28373675
DOI: 10.1038/ijo.2017.90