scholarly journals The role of mitochondria linked fatty-acid uptake-driven adipogenesis in Graves’ Orbitopathy

Endocrinology ◽  
2021 ◽  
Author(s):  
Lei Zhang ◽  
Pavandeep Rai ◽  
Satomi Miwa ◽  
Mohd Shazli Draman ◽  
D Aled Rees ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Culture Medium ◽  
Fatty Acid Uptake ◽  
Therapeutic Interventions ◽  
Acid Uptake ◽  
Atp Production ◽  
Oligomycin A ◽  
Graves Orbitopathy

Abstract Context Depot-specific expansion of orbital-adipose-tissue (OAT) in Graves’ Orbitopathy (GO, an autoimmune condition producing proptosis, visual impairment and reduced quality of life) is associated with fatty-acid (FA) uptake-driven adipogenesis in preadipocytes/fibroblasts (PFs). Objective A role for mitochondria in OAT-adipogenesis in GO. Design, Setting, Participants Confluent PFs from healthy OAT (OAT-H), OAT from GO (OAT-GO) and white-adipose-tissue in culture-medium compared with culture-medium containing a mixed hormonal-cocktail as adipogenic-medium (ADM); or culture-medium containing FA-supplementation, oleate:palmitate:linoleate (45:30:25%) with/without different concentration of mitochondrial bio-substrate ADP/GDP, AICAR (adenosine-analog) or inhibitor oligomycin-A for 17 days. Main outcome measures Oil-Red-O staining and foci-count of differentiated adipocytes for in-vitro adipogenesis; flow-cytometry, relative-QPCR, MTS-assay/10 6 cells, total cellular-ATP detection kit and Seahorse-XFe96-Analyzer for mitochondria and OXPHOS/Glycolysis-ATP production analysis. Results During early adipogenesis before adipocyte formation (day-0,4&7), we observed OAT-specific cellular ATP-production via mitochondrial-OXPHOS in PFs from both OAT-H/OAT-GO, and substantially disrupted OXPHOS-ATP/Glycolysis-ATP production in PFs from OAT-GO, e.g. 40% reduction in OXPHOS-ATP and trend-increased Glycolysis-ATP production on day-4&7 compared with day-0, which contrasted with the stable levels in OAT-H.FA-supplementation in culture-medium triggered adipogenesis in PFs from both OAT-H/OAT-GO, which was substantially enhanced by 1mM GDP reaching 7-18% of ADM-adipogenesis. The FA-uptake-driven adipogenesis was diminished by oligomycin-A but unaffected by treatment with ADP or AICAR. Furthermore, we observed significant positive correlation between FA-uptake-driven adipogenesis by GDP and the ratios of OXPHOS-ATP/Glycolysis-ATP through adipogenesis of PFs from OAT-GO. Conclusions Our study confirmed that FA-uptake can drive OAT-adipogenesis and revealed a fundamental role for mitochondria-OXPHOS in GO development, which provides potential for therapeutic interventions.

scholarly journals Effects of insulin in vitro on lipogenesis and fatty acid uptake in white adipose tissue of Zucker rats aged 10 days

1984 ◽  
Vol 218 (2) ◽  
pp. 653-655 ◽  
Author(s):  
I de Waziers ◽  
E Planche
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Metabolic Pathways ◽  
Fatty Acid Uptake ◽  
Zucker Rats ◽  
Acid Uptake ◽  
Insulin Stimulation ◽  
Tissue Weight ◽  
Adipose Tissue Weight

Adipose-tissue lipogenesis and fatty acid uptake in vitro were higher in obese than in lean Zucker rats aged 10 days. On average, insulin stimulated each of these two metabolic pathways to the same extent in both genotypes. However, in fa/fa pups, we observed that insulin stimulation decreased when adipose-tissue weight increased.

Isotope tracer measures of meal fatty acid metabolism: reproducibility and effects of the menstrual cycle

2005 ◽  
Vol 288 (3) ◽  
pp. E547-E555 ◽  
Author(s):  
Ana Paola Uranga ◽  
James Levine ◽  
Michael Jensen
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Menstrual Cycle ◽  
Dietary Fat ◽  
Fatty Acid Uptake ◽  
Upper Body ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Lower Body

Oxidation and adipose tissue uptake of dietary fat can be measured by adding fatty acid tracers to meals. These studies were conducted to measure between-study variability of these types of experiments and assess whether dietary fatty acids are handled differently in the follicular vs. luteal phase of the menstrual cycle. Healthy normal-weight men ( n = 12) and women ( n = 12) participated in these studies, which were block randomized to control for study order, isotope ([3H]triolein vs. [14C]triolein), and menstrual cycle. Energy expenditure (indirect calorimetry), meal fatty acid oxidation, and meal fatty acid uptake into upper body and lower body subcutaneous fat (biopsies) 24 h after the experimental meal were measured. A greater portion of meal fatty acids was stored in upper body subcutaneous adipose tissue (24 ± 2 vs. 16 ± 2%, P < 0.005) and lower body fat (12 ± 1 vs. 7 ± 1%, P < 0.005) in women than in men. Meal fatty acid oxidation (3H2O generation) was greater in men than in women (52 ± 3 vs. 45 ± 2%, P = 0.04). Leg adipose tissue uptake of meal fatty acids was 15 ± 2% in the follicular phase of the menstrual cycle and 10 ± 1% in the luteal phase ( P = NS). Variance in meal fatty acid uptake was somewhat ( P = NS) greater in women than in men, although menstrual cycle factors did not contribute significantly. We conclude that leg uptake of dietary fat is slightly more variable in women than in men, but that there are no major effects of menstrual cycle on meal fatty acid disposal.

scholarly journals Lipid storage by adipose tissue macrophages regulates systemic glucose tolerance

2014 ◽  
Vol 307 (4) ◽  
pp. E374-E383 ◽  
Author(s):  
Myriam Aouadi ◽  
Pranitha Vangala ◽  
Joseph C. Yawe ◽  
Michaela Tencerova ◽  
Sarah M. Nicoloro ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
Fatty Acid Uptake ◽  
Foam Cell Formation ◽  
Acid Uptake ◽  
Obese Mice ◽  
Adipose Tissue Macrophages

Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance in obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral ATMs in obese mice with siRNA against lipoprotein lipase (LPL), leaving macrophages within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation in visceral adipose tissue of obese mice, consistent with a reduced supply of fatty acids from VLDL hydrolysis. Unexpectedly, silencing LPL also decreased the expression of genes involved in fatty acid uptake (CD36) and esterification in ATMs. This deficit in fatty acid uptake capacity was associated with increased circulating serum free fatty acids. Importantly, ATM LPL silencing also caused a marked increase in circulating fatty acid-binding protein-4, an adipocyte-derived lipid chaperone previously reported to induce liver insulin resistance and glucose intolerance. Consistent with this concept, obese mice with LPL-depleted ATMs exhibited higher hepatic glucose production from pyruvate and glucose intolerance. Silencing CD36 in ATMs also promoted glucose intolerance. Taken together, the data indicate that LPL secreted by ATMs enhances their ability to sequester excess lipid in obese mice, promoting systemic glucose tolerance.

scholarly journals β-Lactoglobulin-linoleate complexes: In vitro digestion and the role of protein in fatty acid uptake

2013 ◽  
Vol 96 (7) ◽  
pp. 4258-4268 ◽  
Author(s):  
Solène Le Maux ◽  
André Brodkorb ◽  
Thomas Croguennec ◽  
Alan A. Hennessy ◽  
Saïd Bouhallab ◽  
...  
Keyword(s):  
Fatty Acid ◽  
In Vitro Digestion ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Β Lactoglobulin

Comparison between Tibetan and Small-tailed Han sheep in adipocyte phenotype, lipid metabolism and energy homoeostasis regulation of adipose tissues when consuming diets of different energy levels

2020 ◽  
Vol 124 (7) ◽  
pp. 668-680
Author(s):  
Xiaoping Jing ◽  
Jianwei Zhou ◽  
Allan Degen ◽  
Wenji Wang ◽  
Yamin Guo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Energy Balance ◽  
Mrna Expression ◽  
Fatty Acid Uptake ◽  
Negative Energy ◽  
Low Energy ◽  
Harsh Environment ◽  
Acid Uptake ◽  
Tibetan Sheep

AbstractThis study aimed to gain insight into how adipose tissue of Tibetan sheep regulates energy homoeostasis to cope with low energy intake under the harsh environment of the Qinghai-Tibetan Plateau (QTP). We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), all wethers and 1·5 years of age, which were each divided randomly into four groups and offered diets of different digestible energy (DE) densities: 8·21, 9·33, 10·45 and 11·57 MJ DE/kg DM. When the sheep lost body mass and were assumed to be in negative energy balance: (1) adipocyte diameter in subcutaneous adipose tissue was smaller and decreased to a greater extent in Tibetan than in Small-tailed Han sheep, but the opposite occurred in the visceral adipose tissue; (2) Tibetan sheep showed higher insulin receptor mRNA expression and lower concentrations of catabolic hormones than Small-tailed Han sheep and (3) Tibetan sheep had lower capacity for glucose and fatty acid uptake than Small-tailed Han sheep. Moreover, Tibetan sheep had lower AMPKα mRNA expression but higher mammalian target of rapamycin mRNA expression in the adipocytes than Small-tailed Han sheep. We concluded that Tibetan sheep had lower catabolism but higher anabolism in adipose tissue and reduced the capacity for glucose and fatty acid uptake to a greater extent than Small-tailed Han sheep to maintain energy homoeostasis when in negative energy balance. These responses provide Tibetan sheep with a high ability to cope with low energy intake and with the harsh environment of the QTP.

scholarly journals Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
T. J. Saari ◽  
J. Raiko ◽  
M. U-Din ◽  
T. Niemi ◽  
M. Taittonen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Brown Adipose

scholarly journals Ovarian Cycle-Specific Regulation of Adipose Tissue Lipid Storage by Testosterone in Female Nonhuman Primates

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4126-4135 ◽  
Author(s):  
Oleg Varlamov ◽  
Michael P. Chu ◽  
Whitney K. McGee ◽  
Judy L. Cameron ◽  
Robert W. O'Rourke ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Sex Hormones ◽  
Luteal Phase ◽  
Fatty Acid Uptake ◽  
Ovarian Cycle ◽  
Lipid Storage ◽  
Hormone Sensitive Lipase ◽  
Acid Uptake ◽  
Hormone Sensitive

Previous studies in rodents and humans suggest that hyperandrogenemia causes white adipose tissue (WAT) dysfunction in females, although the underlying mechanisms are poorly understood. In light of the differences in the length of the ovarian cycle between humans and rodents, we used a nonhuman primate model to elucidate the effects of chronic hyperandrogenemia on WAT function in vivo. Female rhesus macaques implanted with testosterone capsules developed insulin resistance and altered leptin secretion on a high-fat, Western-style diet. In control visceral WAT, lipolysis and hormone-sensitive lipase expression were upregulated during the luteal phase compared with the early follicular (menses) phase of the ovarian cycle. Hyperandrogenemia attenuated elevated lipolysis and hormone-sensitive lipase activity in visceral WAT during the luteal phase but not during menses. Under control conditions, insulin-stimulated Akt and Erk activation and fatty acid uptake in WAT were not significantly affected by the ovarian cycle. In contrast, testosterone treatment preferentially increased fatty acid uptake and insulin signaling at menses. The fatty acid synthase and glucose transporter-4 genes were upregulated by testosterone during the luteal phase. In summary, this study reveals ovarian stage-specific fluctuations in adipocyte lipolysis and suggests that male sex hormones increase and female sex hormones decrease lipid storage in female WAT.

Enhanced fatty acid uptake in visceral adipose tissue is not reversed by weight loss in obese individuals with the metabolic syndrome

Diabetologia ◽  
2014 ◽  
Vol 58 (1) ◽  
pp. 158-164 ◽  
Author(s):  
Marco Bucci ◽  
Anna C. Karmi ◽  
Patricia Iozzo ◽  
Barbara A. Fielding ◽  
Antti Viljanen ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Visceral Adipose Tissue ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
The Metabolic Syndrome ◽  
Visceral Adipose

scholarly journals Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

2013 ◽  
Vol 305 (3) ◽  
pp. E439-E450 ◽  
Author(s):  
Ping Kong ◽  
Carlos Gonzalez-Quesada ◽  
Na Li ◽  
Michele Cavalera ◽  
Dong-Wook Lee ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Weight Gain ◽  
Fatty Acid Uptake ◽  
Cytokine Signaling ◽  
Vascular Density ◽  
Acid Uptake ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes.

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