scholarly journals Lipid Droplet-Anchored Mitochondria Are More Sensitive to Cold in Brown Adipocytes

2020 ◽  
Author(s):  
Mirza Ahmed Hammad ◽  
Liujuan Cui ◽  
Shuyan Zhang ◽  
Pingsheng Liu
Keyword(s):  
Lipid Droplets ◽  
Comparative Proteomics ◽  
Proteomics Analysis ◽  
Futile Cycle ◽  
Brown Adipocytes ◽  
Transport Chain ◽  
Brown Adipose ◽  
C 23 ◽  
Different Temperatures ◽  
Biochemical Analyses

SummaryBrown adipose tissue (BAT) are specialized for uncoupled heat production through mitochondria fueled majorly from fatty acids (FA) of lipid droplets (LDs). How the interaction between the two organelles contributes the generation of heat remains elusive. Here we report that LD-anchored mitochondria (LDAM) were observed in BAT of mice raised at three different temperatures, 30°C, 23°C, and 6°C. The biochemical analyses including Western blotting and electron transport chain subunits showed that LDAM were functional at given temperatures. Comparative proteomics analysis was conducted and revealed that these LDAM had protein level differences from cytoplasmic mitochondria (CM) at different temperatures. Higher expressions of proteins at low temperature were observed for i) FA β-oxidation in LDAM including FA synthesis, and uncoupling, ii) pseudo-futile cycle in CM, and iii) two shuttle systems; glycerol 3-phosphate in both CM and LDAM, and citrate malate in CM. Together, these results suggest that LDs and LDAM are a preorganized and functional organelle complex that permits the rapid response to cold environment.

scholarly journals The effects of melatonin administration in different times of day on the brown adipose tissue in rats with high-calorie diet-induced obesity

2019 ◽  
Vol 77 (1) ◽  
pp. 55-61 ◽  
Author(s):  
O. Kalmykova ◽  
M. Dzerzhynsky
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Optical Density ◽  
Lipid Droplets ◽  
Brown Adipocytes ◽  
Melatonin Administration ◽  
Brown Adipose ◽  
Calorie Diet ◽  
Evening Administration ◽  
High Calorie

The aim of our study was to determine morpho-functional state (area of nucleus, brown adipocytes and also area and number of lipid droplets in each cells, general optical density of tissue) of brown adipose tissue in rats with high-calorie (high fat) dietinduced obesity after melatonin administration in different time of the day (morning and evening). Melatonin was administered daily by gavage for 7 weeks in dose 30 mg/kg either 1 h after lights-on (ZT01) or 1 h before lights-off (ZT11) rats with high-calorie diet (HCD). Besides morphometric parameters as well were measured related visceral fat weight and related brown adipose tissue mass. Rats with HCD had huge changes in brown adipocytes morphology, which summarized in become resembles of classical white adipocytes: grown lipid droplets and cells area, but goes down lipid droplets number and optical density of brown adipose tissue. In general brown adipose tissue with above mentioned characteristic from HCD rats lose their ability to conduct strongly thermoproduction function. After melatonin used in rats with HCD arise leveling of pathological changes, which associated with consumption of HCD. Namely, in groups HCD ZT01 and HCD ZT11 we obtain decreased cells and lipid droplets area, increased lipid droplets number and optical density of brown adipose tissue, in relation to group HCD. Therese received changes has evidence about functionally active brown adipose tissue state, which can also dissipate of exceed energy (lipids – triacylglycerols) amount into whole organism during heat production for avoid to its storage in white adipose tissue and in outside adipose tissue. In addition, evening administration of melatonin (group HCD ZT11) demonstrate more activated state of brown adipose tissueand also related visceral weight gain less, than morning(group HCD ZT01). In conclusions, melatonin influence on morpho-functional state brown adipose tissue in rats with HCD, moreover evening administration can use for obesity therapy via its strong action on activate brown adipocytes.

scholarly journals The ARF-Like GTPase ARFRP1 Is Essential for Lipid Droplet Growth and Is Involved in the Regulation of Lipolysis

2009 ◽  
Vol 30 (5) ◽  
pp. 1231-1242 ◽  
Author(s):  
Angela Hommel ◽  
Deike Hesse ◽  
Wolfgang Völker ◽  
Alexander Jaschke ◽  
Markus Moser ◽  
...  
Keyword(s):  
Lipid Droplet ◽  
Protein Trafficking ◽  
Lipid Droplets ◽  
Hormone Sensitive Lipase ◽  
Droplet Growth ◽  
Brown Adipocytes ◽  
Brown Adipose ◽  
Hormone Sensitive ◽  
Intracellular Organelles ◽  
Adp Ribosylation Factor

ABSTRACT ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a GTPase regulating protein trafficking between intracellular organelles. Here we show that mice lacking Arfrp1 in adipocytes (Arfrp1 ad−/−) are lipodystrophic due to a defective lipid droplet formation in adipose cells. Ratios of mono-, di-, and triacylglycerol, as well as the fatty acid composition of triglycerides, were unaltered. Lipid droplets of brown adipocytes of Arfrp1 ad−/− mice were considerably smaller and exhibited ultrastructural alterations, such as a disturbed interaction of small lipid-loaded particles with the larger droplets, suggesting that ARFRP1 mediates the transfer of newly formed small lipid particles to the large storage droplets. SNAP23 (synaptosomal-associated protein of 23 kDa) associated with small lipid droplets of control adipocytes but was located predominantly in the cytosol of Arfrp1 ad−/− adipocytes, suggesting that lipid droplet growth is defective in Arfrp1 ad−/− mice. In addition, levels of phosphorylated hormone-sensitive lipase (HSL) were elevated, and association of adipocyte triglyceride lipase (ATGL) with lipid droplets was enhanced in brown adipose tissue from Arfrp1 ad−/− mice. Accordingly, basal lipolysis was increased after knockdown of Arfrp1 in 3T3-L1 adipocytes. The data indicate that disruption of ARFRP1 prevents the normal enlargement of lipid droplets and produces an activation of lipolysis.

Morphometric-stereologic analysis of brown adipocyte differentiation in adult mice

1992 ◽  
Vol 262 (4) ◽  
pp. C1018-C1023 ◽  
Author(s):  
F. Goglia ◽  
A. Geloen ◽  
A. Lanni ◽  
Y. Minaire ◽  
L. J. Bukowiecki
Keyword(s):  
Surface Density ◽  
Lipid Droplets ◽  
Adipocyte Differentiation ◽  
Interstitial Cells ◽  
Brown Adipocyte ◽  
Inner Mitochondrial Membrane ◽  
Brown Adipocytes ◽  
Blood Capillaries ◽  
Adult Mice ◽  
Brown Adipose

Brown adipocyte differentiation from interstitial stem cells was analyzed by morphometric-stereologic methods in adult mice. Confirming previous studies, four different stages of development were identified: 1) interstitial cells----2) protoadipocytes (interstitial cells with tiny lipid droplets)----3) preadipocytes----4) mature brown adipocytes. Brown adipocyte precursor cells (interstitial cells and protoadipocytes) occupied only a small fraction of total brown adipose tissue (BAT) volume (1.7 and 1.8%, respectively). Most of the BAT volume was occupied by fully differentiated multilocular cells (65% vol/vol), preadipocytes (12%), and blood capillaries (10%). The differentiation of protoadipocytes into preadipocytes was characterized by a doubling in the cellular volume (from 800 to 1,500 microns 3) that was associated with a fivefold increase in the number of mitochondria (221 to 1,464), an eightfold augmentation in mitochondrial size (from 0.042 to 0.37 microns 3), a fourfold increase in the surface density of the inner mitochondrial membrane (from 8 to 35 microns 2/microns 3), resulting in a 14-fold enlargement in the relative volume of the mitochondrial compartment (from 2 to 29%). This remarkable mitochondrial proliferation was accompanied by an increase in the number and volume of cytosolic lipid droplets. In contrast, the differentiation of preadipocytes into brown adipocytes was mainly characterized by a doubling in the size of the lipid compartment; the mean volume of single droplets increased 35 times but their number decreased 6-7 times. The mitochondrial modifications were minor; there was only a slight increase in the surface density of the inner membrane. In conclusion, the major step of brown adipocyte differentiation consists in the transformation of protoadipocytes into preadipocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Lipid Droplets in Brown Adipose Tissue Are Dispensable for Cold-Induced Thermogenesis

2020 ◽  
Author(s):  
Chandramohan Chitraju ◽  
Alexander Fischer ◽  
Robert V. Farese ◽  
Tobias C. Walther
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Lipid Droplets ◽  
Metabolic Energy ◽  
Brown Adipocyte ◽  
Glucose Disposal ◽  
Brown Adipocytes ◽  
Brown Adipose

SUMMARYBrown adipocytes store metabolic energy as triglycerides (TG) in multilocular lipid droplets (LDs). Fatty acids released from brown adipocyte LDs by lipolysis are thought to activate and fuel UCP1-mediated thermogenesis. Here we test this hypothesis by preventing fatty acid storage in murine brown adipocytes through brown adipose tissue (BAT)-specific deletions of the TG synthesis enzymes, DGAT1 and DGAT2 (BA-DGAT KO). Despite the absence of LDs, BA-DGAT KO mice had functional BAT and maintained euthermia during acute or chronic cold exposure. As apparent adaptations to the lack of TG, brown adipocytes of BA-DGAT KO mice appear to utilize circulating glucose and fatty acids, as well as stored glycogen to fuel thermogenesis. Moreover, BA-DGAT KO mice were resistant to diet-induced glucose intolerance, likely due to increased glucose disposal by BAT. Thus, surprisingly, TGs in BAT are dispensable for its function, in part through adaptations to utilize other fuel sources.

scholarly journals Cold-induction of afadin in brown fat supports its thermogenic capacity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morten Lundh ◽  
Ali Altıntaş ◽  
Marco Tozzi ◽  
Odile Fabre ◽  
Tao Ma ◽  
...  
Keyword(s):  
Cold Exposure ◽  
Functional Enrichment ◽  
Activation Process ◽  
Target Tissue ◽  
Cold Stimulation ◽  
Brown Adipocytes ◽  
Protein Levels ◽  
Mrna Induction ◽  
Metabolic Functions ◽  
Brown Adipose

AbstractThe profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Cold exposure acutely increases Afadin protein levels and its phosphorylation in BAT. Knockdown of Afadin in brown pre-adipocytes does not alter adipogenesis but restricts β3-adrenegic induction of thermogenic genes expression and HSL phosphorylation in mature brown adipocytes. Consistent with a defect in thermogenesis, an impaired cold tolerance was observed in fat-specific Afadin knockout mice. However, while Afadin depletion led to reduced Ucp1 mRNA induction by cold, stimulation of Ucp1 protein was conserved. Transcriptomic analysis revealed that fat-specific ablation of Afadin led to decreased functional enrichment of gene sets controlling essential metabolic functions at thermoneutrality in BAT, whereas it led to an altered reprogramming in response to cold, with enhanced enrichment of different pathways related to metabolism and remodeling. Collectively, we demonstrate a role for Afadin in supporting the adrenergic response in brown adipocytes and BAT function.

Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via Hypoxia-Inducible Factor-1α

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
Tetsuhiro Horie ◽  
Kazuya Fukasawa ◽  
Takashi Iezaki ◽  
Gyujin Park ◽  
Yuki Onishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypoxia Inducible Factor ◽  
Amino Acid Transporters ◽  
Hypoxic Stress ◽  
Gene Encoding ◽  
Brown Adipocytes ◽  
Hypoxia Inducible Factor 1Α ◽  
Brown Adipose

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxia-inducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia-responsive gene in brown adipocytes.

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