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Endocrinology and Metabolism Clinics of... Jun 2020Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number... (Review)
Review
Regional adipose tissue distribution differs between men and women. Differences in the accumulation of adipose tissue as well as the regulation of secretion of a number of products from adipose tissue are under the control of sex steroids, which act through a wide variety of mechanisms, both direct and indirect, to tailor metabolism to the unique needs of each sex. A fuller understanding of sex-based differences in adipose tissue function may help with tailored strategies for disease prevention and treatment and provide insights into fundamental differences in the processes that regulate nutrient homeostasis and body weight.
Topics: Adipogenesis; Adiponectin; Adipose Tissue; Adult; Estrogens; Female; Humans; Leptin; Lipolysis; Male; Sex Characteristics; Testosterone
PubMed: 32418585
DOI: 10.1016/j.ecl.2020.02.008 -
Cells Dec 2022The single nucleotide polymorphism I148M of the lipase () is associated with an unfavorable prognosis in alcoholic and non-alcoholic steatohepatitis (ASH, NASH), with...
The single nucleotide polymorphism I148M of the lipase () is associated with an unfavorable prognosis in alcoholic and non-alcoholic steatohepatitis (ASH, NASH), with progression to liver cirrhosis and development of hepatocellular carcinoma. In this study, we investigated the mechanistic interaction of PNPLA3 with lipid droplet (LD)-associated proteins of the perilipin family, which serve as gatekeepers for LD degradation. In a collective of 106 NASH, ASH and control liver samples, immunohistochemical analyses revealed increased ballooning, inflammation and fibrosis, as well as an accumulation of PNPLA3-perilipin 5 complexes on larger LDs in patients homo- and heterozygous for PNPLA3(I148M). Co-immunoprecipitation demonstrated an interaction of PNPLA3 with perilipin 5 and the key enzyme of lipolysis, adipose triglyceride lipase (ATGL). Localization studies in cell cultures and human liver showed colocalization of perilipin 5, ATGL and PNPLA3. Moreover, the lipolytic activity of ATGL was negatively regulated by PNPLA3 and perilipin 5, whereas perilipin 1 displaced PNPLA3 from the ATGL complex. Furthermore, ballooned hepatocytes, the hallmark of steatohepatitis, were positive for PNPLA3 and perilipins 2 and 5, but showed decreased perilipin 1 expression with respect to neighboured hepatocytes. In summary, PNPLA3- and ATGL-driven lipolysis is significantly regulated by perilipin 1 and 5 in steatohepatitis.
Topics: Humans; Lipolysis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Perilipin-1; Perilipin-5
PubMed: 36611868
DOI: 10.3390/cells12010073 -
Cell Metabolism Sep 2021Appropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics and thus represents a crucial process for cellular metabolic adaptations....
Appropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics and thus represents a crucial process for cellular metabolic adaptations. Here, we show that mitochondrial cristae architecture and expression of the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons, which are key metabolic sensors implicated in energy balance control, is affected by fluctuations in nutrient availability. Genetic inactivation of OPA1 in POMC neurons causes dramatic alterations in cristae topology, mitochondrial Ca handling, reduction in alpha-melanocyte stimulating hormone (α-MSH) in target areas, hyperphagia, and attenuated white adipose tissue (WAT) lipolysis resulting in obesity. Pharmacological blockade of mitochondrial Ca influx restores α-MSH and the lipolytic program, while improving the metabolic defects of mutant mice. Chemogenetic manipulation of POMC neurons confirms a role in lipolysis control. Our results unveil a novel axis that connects OPA1 in POMC neurons with mitochondrial cristae, Ca homeostasis, and WAT lipolysis in the regulation of energy balance.
Topics: Adipose Tissue; Animals; GTP Phosphohydrolases; Homeostasis; Lipolysis; Mice; Neurons; Pro-Opiomelanocortin
PubMed: 34343501
DOI: 10.1016/j.cmet.2021.07.008 -
Biochimica Et Biophysica Acta.... Oct 2017The discovery of adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) provided a major paradigm shift in the understanding... (Review)
Review
The discovery of adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) provided a major paradigm shift in the understanding of intracellular lipolysis in both adipocytes and nonadipocyte cells. The subsequent discovery of G0/G1 switch gene 2 (G0S2) as a potent endogenous inhibitor of ATGL revealed a unique mechanism governing lipolysis and fatty acid (FA) availability. G0S2 is highly conserved in vertebrates, and exhibits cyclical expression pattern between adipose tissue and liver that is critical to lipid flux and energy homeostasis in these two tissues. Biochemical and cell biological studies have demonstrated that a direct interaction with ATGL mediates G0S2's inhibitory effects on lipolysis and lipid droplet degradation. In this review we examine evidence obtained from recent in vitro and in vivo studies that lends support to the proof-of-principle concept that G0S2 functions as a master regulator of tissue-specific balance of TG storage vs. mobilization, partitioning of metabolic fuels between adipose and liver, and the whole-body adaptive energy response. This article is part of a Special Issue entitled: Recent Advances in Lipid Droplet Biology edited by Rosalind Coleman and Matthijs Hesselink.
Topics: Adipose Tissue; Animals; Cell Cycle Proteins; Energy Metabolism; Fatty Acids; Humans; Lipase; Lipid Droplets; Lipolysis; Liver; Organ Specificity; Triglycerides
PubMed: 28645852
DOI: 10.1016/j.bbalip.2017.06.007 -
Trends in Endocrinology and Metabolism:... Oct 2016The selective breakdown by autophagy of lipid droplet (LD)-stored lipids, termed lipophagy, is a lysosomal lipolytic pathway that complements the actions of cytosolic... (Review)
Review
The selective breakdown by autophagy of lipid droplet (LD)-stored lipids, termed lipophagy, is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. The physiological importance of lipophagy has been demonstrated in multiple mammalian cell types, as well as in lower organisms, and this pathway has many functions in addition to supplying free fatty acids to maintain cellular energy stores. Recent studies have begun to delineate the molecular mechanisms of the selective recognition of LDs by the autophagic machinery, as well as the intricate crosstalk between the different forms of autophagy and neutral lipases. These studies have led to increased interest in the role of lipophagy in both human disease pathogenesis and therapy.
Topics: Animals; Autophagy; Humans; Lipid Droplets; Lipid Metabolism; Lipolysis; Perilipin-1
PubMed: 27365163
DOI: 10.1016/j.tem.2016.06.003 -
Current Opinion in Pharmacology Dec 2022Metabolism consists of life-sustaining chemical reactions involving metabolites. Historically, metabolites were defined as the intermediates or end products of... (Review)
Review
Metabolism consists of life-sustaining chemical reactions involving metabolites. Historically, metabolites were defined as the intermediates or end products of metabolism and considered to be passive participants changed by metabolic processes. However, recent research has redefined how we view metabolism. There is emerging evidence of metabolites which function to mediate cellular signalling and interorgan crosstalk, regulating local metabolism and systemic physiology. These bioactive metabolite signals have been termed metabokines. Metabokines regulate diverse energy metabolism pathways across multiple tissues, including fatty acid β-oxidation, mitochondrial oxidative phosphorylation, lipolysis, glycolysis and gluconeogenesis. There is increasing impetus to uncover novel metabokine signalling axes to better understand how these may be perturbed in metabolic diseases and determine their utility as therapeutic targets.
Topics: Humans; Energy Metabolism; Glycolysis; Lipolysis; Mitochondria
PubMed: 36137304
DOI: 10.1016/j.coph.2022.102286 -
Frontiers in Endocrinology 2023Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in...
BACKGROUND
Stromal adipocytes and tumor breast epithelial cells undergo a mutual metabolic adaptation within tumor microenvironment. Therefore, browning and lipolysis occur in cancer associated adipocytes (CAA). However, the paracrine effects of CAA on lipid metabolism and microenvironment remodeling remain poorly understood.
METHODS
To analyze these changes, we evaluated the effects of factors in conditioned media (CM) derived from explants of human breast adipose tissue from tumor (hATT) or normal (hATN) on morphology, degree of browning, the levels of adiposity, maturity, and lipolytic-related markers in 3T3-L1 white adipocytes by Western blot, indirect immunofluorescence and lipolytic assay. We analyzed subcellular localization of UCP1, perilipin 1 (Plin1), HSL and ATGL in adipocytes incubated with different CM by indirect immunofluorescence. Additionally, we evaluated changes in adipocyte intracellular signal pathways.
RESULTS
We found that adipocytes incubated with hATT-CM displayed characteristics that morphologically resembled beige/brown adipocytes with smaller cell size and higher number of small and micro lipid droplets (LDs), with less triglyceride content. Both, hATT-CM and hATN-CM, increased Pref-1, C/EBPβ LIP/LAP ratio, PPARγ, and caveolin 1 expression in white adipocytes. UCP1, PGC1α and TOMM20 increased only in adipocytes that were treated with hATT-CM. Also, hATT-CM increased the levels of Plin1 and HSL, while decreased ATGL. hATT-CM modified the subcellular localization of the lipolytic markers, favoring their relative content around micro-LDs and induced Plin1 segregation. Furthermore, the levels of p-HSL, p-ERK and p-AKT increased in white adipocytes after incubation with hATT-CM.
CONCLUSIONS
In summary, these findings allow us to conclude that adipocytes attached to the tumor could induce white adipocyte browning and increase lipolysis as a means for endocrine/paracrine signaling. Thus, adipocytes from the tumor microenvironment exhibit an activated phenotype that could have been induced not only by secreted soluble factors from tumor cells but also by paracrine action from other adipocytes present in this microenvironment, suggesting a "domino effect".
Topics: Humans; Lipolysis; Adipocytes, White; Adipose Tissue; Lipid Metabolism; Adipocytes, Brown; Perilipin-1
PubMed: 37181035
DOI: 10.3389/fendo.2023.1144016 -
Biomolecules Dec 2021The liver is extremely active in oxidizing triglycerides (TG) for energy production. An imbalance between TG synthesis and hydrolysis leads to metabolic disorders in the... (Review)
Review
The liver is extremely active in oxidizing triglycerides (TG) for energy production. An imbalance between TG synthesis and hydrolysis leads to metabolic disorders in the liver, including excessive lipid accumulation, oxidative stress, and ultimately liver damage. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme that catalyzes the first step of TG breakdown to glycerol and fatty acids. Although its role in controlling lipid homeostasis has been relatively well-studied in the adipose tissue, heart, and skeletal muscle, it remains largely unknown how and to what extent ATGL is regulated in the liver, responds to stimuli and regulators, and mediates disease progression. Therefore, in this review, we describe the current understanding of the structure-function relationship of ATGL, the molecular mechanisms of ATGL regulation at translational and post-translational levels, and-most importantly-its role in lipid and glucose homeostasis in health and disease with a focus on the liver. Advances in understanding the molecular mechanisms underlying hepatic lipid accumulation are crucial to the development of targeted therapies for treating hepatic metabolic disorders.
Topics: Adipose Tissue; Lipase; Lipolysis; Liver; Triglycerides
PubMed: 35053204
DOI: 10.3390/biom12010057 -
Biochimica Et Biophysica Acta.... May 2022Adipose tissue is a critical organ for nutrient sensing, energy storage and maintaining metabolic health. The failure of adipose tissue homeostasis leads to metabolic... (Review)
Review
Adipose tissue is a critical organ for nutrient sensing, energy storage and maintaining metabolic health. The failure of adipose tissue homeostasis leads to metabolic disease that is seen during obesity or aging. Local metabolic processes are coordinated by interacting microenvironments that make up the complexity and heterogeneity of the adipose tissue. Catecholamine-induced lipolysis, a critical pathway in adipocytes that drives the release of stored triglyceride as free fatty acid after stimulation, is impaired during aging. The impairment of this pathway is associated with a failure to maintain a healthy body weight, core body-temperature during cold stress or mount an immune response. Along with impairments in aged adipocytes, aging is associated with an accumulation of inflammation, immune cell activation, and increased dysfunction in the nervous and lymphatic systems within the adipose tissue. Together these microenvironments support the initiation of stimulated lipolysis and the transport of free fatty acid under conditions of metabolic homeostasis. However, during aging, the defects in these cellular systems result in a reduction in ability to stimulate lipolysis. This review will focus on how the immune, nervous and lymphatic systems interact during tissue homeostasis, review areas that are impaired with aging and discuss areas of research that are currently unclear.
Topics: Adipocytes; Adipose Tissue; Fatty Acids, Nonesterified; Lipolysis
PubMed: 35131468
DOI: 10.1016/j.bbalip.2022.159118 -
Nutrients Jul 2023Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main...
Besides their common use as an adaptogen, (Willd.) Iljin. rhizome and its root extract (RCE) are also reported to beneficially affect lipid metabolism. The main characteristic secondary metabolites of RCE are phytoecdysteroids. In order to determine an RCE's phytoecdysteroid profile, a novel, sensitive, and robust high-performance thin-layer chromatography (HPTLC) method was developed and validated. Moreover, a comparative analysis was conducted to investigate the effects of RCE and its secondary metabolites on adipogenesis and adipolysis. The evaluation of the anti-adipogenic and lipolytic effects was performed using human Simpson-Golabi-Behmel syndrome cells, where lipid staining and measurement of released glycerol and free fatty acids were employed. The HPTLC method confirmed the presence of 20-hydroxyecdysone (20E), ponasterone A (PA), and turkesterone (TU) in RCE. The observed results revealed that RCE, 20E, and TU significantly reduced lipid accumulation in human adipocytes, demonstrating their anti-adipogenic activity. Moreover, RCE and 20E were found to effectively stimulate basal lipolysis. However, no significant effects were observed with PA and TU applications. Based on our findings, RCE and 20E affect both lipogenesis and lipolysis, while TU only restrains adipogenesis. These results are fundamental for further investigations.
Topics: Humans; Mice; Animals; Adipogenesis; Leuzea; Plant Extracts; Lipid Metabolism; Lipolysis; Lipids; 3T3-L1 Cells
PubMed: 37447387
DOI: 10.3390/nu15133061