Visceral Fat Cells Research Articles

SARS-CoV-2 infects adipose tissue in a fat depot- and viral lineage-dependent manner

Visceral adiposity is a risk factor for severe COVID-19, and a link between adipose tissue infection and disease progression has been proposed. Here we demonstrate that SARS-CoV-2 infects human adipose tissue and undergoes productive infection in fat cells. However, susceptibility to infection and the cellular response depends on the anatomical origin of the cells and the viral lineage. Visceral fat cells express more ACE2 and are more susceptible to SARS-CoV-2 infection than their subcutaneous counterparts. SARS-CoV-2 infection leads to inhibition of lipolysis in subcutaneous fat cells, while in visceral fat cells, it results in higher expression of pro-inflammatory cytokines. Viral load and cellular response are attenuated when visceral fat cells are infected with the SARS-CoV-2 gamma variant. A similar degree of cell death occurs 4-days after SARS-CoV-2 infection, regardless of the cell origin or viral lineage. Hence, SARS-CoV-2 infects human fat cells, replicating and altering cell function and viability in a depot- and viral lineage-dependent fashion.

Gain without pain: beyond sport effortless exercise solutions

Ageing is associated with decreased metabolism, increased toxicity, decreased skeletal muscle mass (SMM) and increased visceral fat deposits that compromise the normal functioning of vital organs such as the liver, pancreas and intestines, increasing the risk of a number of health problems, including type 2 diabetes, coronary heart disease, hypertension and non-alcoholic fatty liver. Visceral adipose tissue holds large amounts of toxins that alter thyroid hormone metabolism, lowering resting metabolic rate (RMR). Strenuous physical exercise can reach these deeper visceral adipose tissue layers. However, excessive exercise is necessary to reduce visceral adipose tissue elevates cortisol while decreasing testosterone. The hormonal imbalance resulting from this inverse cortisol/testosterone relationship ultimately leads to weight gain, despite all the efforts invested in physical activity. On the other hand, lack of exercise allows for accumulation of toxicity and increased vulnerability to chronic physical disorders. Energy-based technologies report successful results in reducing subcutaneous fat layers; however, data is not currently available about methods that can reduce deeper visceral adipose tissue and relieve the system from visceral fat cells stuffed with excess triglycerides. In this study, we examined hormone and cholesterol fluctuations in the blood tests of eight subjects undergoing six 45 minutes of effortless exercise sessions with a novel London University invention. We also explored changes in their visceral adipose tissue, overall body fat mass, SMM, basic metabolic rate (BMR), waist and abdomen reduction in centimetres (cm) and overall weight loss in kilograms (kg). Subjects' results revealed a statistically significant increase in triiodothyronine (Free T3), accompanied by a significant decrease in the very low-density lipoprotein (VLDL) and triglycerides. Cortisol did not show statistically significant fluctuations. There was a statistically significant decrease in visceral adipose tissue and overall body fat mass and a statistically significant increase in SMM. Waist and abdomen cm loss, and weight loss in kgs were statistically significant, demonstrating a substantial decrease in cm and kgs in all subjects that persisted a week after the last treatment. Results of this study supported the hypothesis that this method of effortless exercise can reduce both overall body fat mass, visceral adipose tissue and VLDL, while increasing SMM and the metabolic hormone free T3, without the aid of diet or change in lifestyle.

1712-P: HIV-1 Vpr Couples Metabolic Inflexibility with White Adipose Tissue Thermogenesis

The HIV accessory protein Vpr contributes to cardinal metabolic defects noted in persons living with HIV (PLWH), including accelerated lipolysis, impaired fatty acid oxidation, slowed fatty acid export, and steatohepatitis (Agarwal et al, Sci Trans Med 2017). PLWH also manifest “beiging” and markers of thermogenesis within some white adipose tissue (WAT) depots, but paradoxically these changes correlate with decreased insulin sensitivity and hyperlipidemia. We sought to determine whether Vpr activity affects thermogenesis and the dynamics of beiging in two Vpr mouse models. UCP1 expression was strongly increased in subcutaneous fat of Vpr mice and showed equivalent copy number in WAT biopsies from PLWH. Histology confirmed browning of subcutaneous but not visceral WAT in the Vpr mouse models. Adipocytes derived from these depots showed increased oxygen consumption rate in subcutaneous but not visceral fat cells, also strongly indicative of beiging. Measurements of energy balance indicated Vpr mice display metabolic inflexibility and cannot shift efficiently from carbohydrates to fat during day-night cycles. Furthermore, Vpr mice mice showed a marked inability to defend body temperature when exposed to 4oC for 6 hours. Thus HIV-1 Vpr disrupts metabolic efficiency coupled with maladaptive subcutaneous WAT beiging. These data suggest an expanded role for Vpr in the pathogenesis of HIV-associated metabolic disorders. Disclosure N. Agarwal: None. P. Saha: None. S.M. Hartig: None. A. Balasubramanyam: None. Funding National Institutes of Health (R21/R33AI116208)

INSULIN RESISTANCE IS AN ALIMENTARY DEFICIENCY OF ENERGY SUBSTRATES (GLUCOSE) IN THE BIOLOGICAL REACTION OF EXOTROPHY AND APHYSIOLOGY COMPENSATION BY FATTY ACIDS VIA THE BIOLOGICAL REACTION OF ENDOTHROPHY

The deficiency of energy substrates in the biological function of trophology and biological reaction of exotrophy is formed by two factors. Excess of meat in the diet leads to high content of palmitic fatty acid (FA) in hepatocytes and formation of palmitic triglycerides (TG). Post heparin lipoprotein lipase slowly hydrolyzes palmitic TG in blood plasma lipoproteins and releases small amounts of FA. If dietary carbohydrate content is low, the biological function of exotrophy does not provide the substrate from which hepatocytes can rapidly produce oleic nonesterified FA de novo. Energy substrate deficiency activates the biological function of adaptation and the biological reaction of compensation. Under the effect of epinephrin NEFA deficiency is compensated via the biological reaction of endotrophy and lipolysis in omental visceral fat cells. In insulin resistance (IR) syndrome, the biological function of feeding is realized nonphysiologically while the biological reaction of adaptation is realized physiologically. An increase in NEFA blood content physiologically blocks glucose uptake in cells. Biological role of insulin consists in conversion of distant ocean-living carnivorous (fish-eating) ancestors of Homo sapiens with palmitic type of FA metabolism into herbivorous dry land-living species with oleic type metabolism of FA. The IR syndrome can be normalized. To this end a) the patient's will to activate the cognitive biological function (intellect) and b) comprehension of the fact that phylogenetically dry land-living Homo sapiens has developed as a herbivorous but not carnivorous species. Concerning death rate, cardiovascular pathologies are dominating in populations of many countries, while feeding function disorders prevail in frequency. These disorders form the pathophysiological basis for all metabolic pandemias: 1) atherosclerosis and atheromatosis, 2) essential arterial hypertension, 3) metabolic syndrome, 4) obesity, 5) insulin resistance syndrome, 6) nonalcoholic fatty liver disease, and 7) endogenous hyperuricemia. Persistent potential deficiency of energy for realization of all biological reactions and functions is the major metabolic disorders in diabetes mellitus. Insulin resistance is a pathology associated primarily with FA and secondarily with glucose.

Physiological concentrations of β-hydroxybutyrate do not promote adipocyte browning

AimsPrevious work has demonstrated that ketogenic diets promote white fat browning; however, the exact mechanisms underlying this phenomenom have yet to be elucidated. Recently, an in vitro study showed that supraphysiological concentrations of β-hydroxybutyrate (βHB) had a strong influence on the induction of adipocyte browning. On the other hand, concentrations in the physiological range, achieved through ketogenic diets and prolonged fasting produce values of 1–3 mM and 4–7 mM, respectively. Herein, we investigated the impact of physiological concentrations of βHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues. Main methodsThe effects of βHB on adipocyte browning were investigated in vitro, using primary cultures of isolated visceral and subcutaneous fat cells and cultured 3T3-L1 adipocytes, and in vivo. Key findingsIt was determined that βHB failed to induce changes in the oxidative capacity, citrate synthase activity or browning gene expression patterns in isolated adipocytes, and did not exert a permissive effect on β-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following βHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after βHB salt treatment. Rats administered βHB salts also presented reduced brown adipose tissue UCP1 protein expression. SignificanceThe mechanisms underlying ketogenic diet-induced browning of adipocytes are not known. The results from the present study indicate that physiological concentrations of βHB are not responsible for this phenomenon, despite the observed βHB-mediated downregulation of UCP1 expression.

Laurine fatty acids, medium fatty acids and triglycerides, hyperlipidemia, resistance to insulin, prevention of atherosclerosis and ateromatosis.

Although the biochemistry of the positive effects of medium-chain fatty acids (FA) and triglycerides (TG) of the same name in vivo is not fully understood, food enriched with medium-chain LC and the same TG is effective in patients with type I diabetes, insulin resistance syndrome and in neurodegenerative pathology. Lauric C12 LC is half the FA in coconut oil. Residents of southeast Asia with constant use of coconut oil, have a low level of diseases of the cardiovascular system in the population. With a regulatory intake with food C12:0 laurin FA formed moderate ketosis and neuroprotective effect. Unlike long-chain LC, medium-chain TG cells are not deposited either in visceral fat cells, or in insulin-dependent adipocytes. Medium-chain fatty acids rapidly oxidize mitochondria; the formation of acetyl-CoA cells is used to form ketone bodies, activating thermogenesis in orange and brown adipocytes. Experiments with animals and observations in the clinic showed that taking medium-chain TG with food is more physiological than long-chain oils. This significantly increases the level of cholesterol in high-density lipoproteins. Food enriched with medium chain TG is optimal for increasing the ketone content in blood plasma, cerebrospinal fluid without limiting the carbohydrate content in food. The formation of excess ketone bodies by cells can be achieved by activating the metabolic transformations of medium-chain FAs, without fasting and preserving carbohydrates in food. Coconut oil has a positive effect on the cardiovascular system, preventing the formation of atherosclerosis and atheromatosis. Effective in the prevention of the pathology of the cardiovascular system is a decrease in food amounts of palmitic acid, an increase in oleic acid, polyene FA with a simultaneous increase in the proportion of medium-chain FA.

The activity of transient receptor potential channel C-6 modulates the differentiation of fat cells.

Previously, the V1-3 isoforms of the transient receptor potential channel (TRP) have been shown to promote or prevent adipocyte differentiation. In the current study, the C isoforms were screened for blocking adipogenesis. The hypothesis that the TRP classic or canonical (TRPC) deters adipocyte differentiation was investigated in 3T3-L1 cells employing the channel-specific activator and antagonist, silencing, and overexpression techniques. Fat accumulation in cells was visualized by Oil Red O staining. Intracellular calcium inflow was estimated by confocal microscopy. A high-fat (HF) feeding study was also performed on C57BL/6J mice to verify the findings in the cell model. Among the 6 C isoforms tested, only TRPC-6 inhibited the differentiation of fat cells. The phytochemical quercetin induced the channel protein expression. Calcium-imaging results also revealed that the flavonoid could trigger calcium inflow. Coadministration of quercetin (1 or 20 mg/kg body weight) in an HF diet prevented TRPC-6 from declining and attenuated phosphorylated (p)-PKB and PI3k, as well as the proliferation of visceral fat cells. The present study illustrated that TRPC-6 activation could perturb adipocyte differentiation. The food flavonoid quercetin was a TRPC-6 inducer and activator and it could prevent adipogenesis in mice.-Tan, Y. Q., Kwan, H. Y., Yao, X., Leung, L. K. The activity of transient receptor potential channel C-6 modulates the differentiation of fat cells.

GLP-1 Improves Adipocyte Insulin Sensitivity Following Induction of Endoplasmic Reticulum Stress.

Glucagon-like peptide 1 (GLP-1) improves insulin resistance of adipose tissue in obese humans. However, the mechanism of this effect is unclear. Perturbation of endoplasmic reticulum (ER) homeostasis impairs insulin signaling. We hypothesized that GLP-1 could directly improve insulin signaling in ER-stressed adipocytes. Here, we examined the effects of GLP-1 on ER stress response in fat cells in an obese and insulin-resistant murine model. We found that GLP-1 analog liraglutide reduced ER stress related gene expression in visceral fat cells accompanied by improved systemic insulin tolerance. Consistently, GLP-1 decreased CHOP expression and increased insulin stimulated AKT phosphorylation (p-AKT) in thapsigargin, a ER stress inducer, treated white fat cells differentiated from visceral stromal vascular fraction. We further found blocking CHOP expression increased insulin stimulated p-AKT in ER-stressed fat cells. Of note, we found mTOR signaling pathway contributed to the expression of ATF4 and subsequently the CHOP expression in ER stress response, while GLP-1 inhibited mTOR activity as exemplified by elevated autophagosome formation and increased LC3II/LC3I ratio. These findings suggest that GLP-1 directly modulates the ER stress response partially via inhibiting mTOR signaling pathway, leading to increased insulin sensitivity in adipocytes.

Early adipogenesis contributes to excess fat accumulation in cave populations of Astyanax mexicanus

Cavefish populations of Astyanax mexicanus have increased body fat compared to surface fish populations of the same species when fed ad libitum in the laboratory. We have previously shown that some cavefish populations display hyperphagia (elevated appetite) to increase food consumption, fat deposition and starvation resistance. However, not all cavefish populations display hyperphagia, yet all previously tested cavefish display elevated body fat levels. Here we have extended this analysis by focusing on visceral fat acquisition in three independently derived cavefish populations. We show that cavefish from two independently derived cavefish populations (Pachón and Tinaja) display increased amounts of visceral adipose tissue (VAT) due to hypertrophy of visceral adipocytes while Molino cavefish display hypertrophy but only slightly elevated VAT levels compared to surface fish. Furthermore, we show that Pachón and Tinaja cavefish develop increased VAT even when food intake is matched to surface fish, suggesting appetite independent mechanisms. We show that in the Pachón population, the differences in the visceral fat in adults correlates with changes in the timing of visceral development, making a developmental contribution likely. Visceral fat development in surface fish starts between 10 and 11 dpf, while in Pachón cavefish, visceral fat cells become visible as early as 8 dpf and develop significantly higher amounts of lipid droplets before surface fish start visceral fat accumulation. We further show that this developmental difference is unique to the Pachón cavefish population, while the Tinaja cavefish population - which displays hyperphagia - starts to develop visceral fat similar to surface fish. We suggest the differences in early adipogenesis in the Pachón population as an additional strategy of increased fat gain in cavefish to adapt to food scarcity.

Biological role of insulin: transformation of carnivores leaving in the ocean into herbivores living on the dry land. Development of the biological function of locomotion and kinetic parameters of the body.

Phylogenetic theory of general pathology draws researchers' attention to the following aspects of the biological effects of insulin. 1. Phylogenetically, in vivo insulin is primarily involved in the metabolism of fatty acids (FA) and only in the second turn in glucose metabolism; regulation of FA metabolism in cells started millions of years earlier than that of glucose metabolism. Phylogenetically late insulin blocks lipolysis only in phylogenetically late insulin-dependent subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. 2. Biological role of insulin consists in the formation of the biological function of locomotion, i.e., movement arising from contraction of striated myocytes provided with substrates (FA and glucose) for energy production as macroergic ATP. 3. Biological destiny of phylogenetically late insulin is transformation of carnivorous (fish-eating) animals living in the ocean into herbivores living on the dry land. 4. Insulin has formed in vivo highly efficient oleic variant of FA metabolism instead of phylogenetically early less efficient palmitic variant. 5. Biologically, insulin is destined for providing cells with energy and perfection of physical activity and kinetic parameters of the organism. According to phylogenetic theory of general pathology and basic principles of endocrinology, clinical cases should be regarded as: 1. rare structurally-related insulindeficient type I diabetes mellitus, 2. rare structurally-related (receptor pathology) hyperinsulinemic type II diabetes mellitus, and 3. a great number of patients with functional disorders in the hormone activity, insulin resistance syndrome, metabolic syndrome and obesity. We believe that the food of herbivores should contain palmitic acid in the amounts that hepatocytes can esterify into oleic very low density lipoproteins and cells can internalize as ligand oleic by apoЕ/В-100 endocytosis without formation of low density lipoproteins.

Insulin resistance: the conflict between biological settings of energy metabolism and human lifestyle (a glance at the problem from evolutionary viewpoint)

A biological function of the phylogenetically late humoral mediator insulin is to provide energy substrates for locomotion, i.e. movement resulting from contraction of striated muscles. Insulin is able to meet this evolutionary demand of an organism by means of the effective ATP production in the mitochondria. Exogenous fatty acids, optimised endogenous fatty acids produced from glucose and glucose itself are the major substrates for ATP synthesis. Cells stimulated by insulin produce ω-9 С18:1 oleic acid from glucose. This fatty acid is oxidised by the mitochondria at a higher rate than exogenous and endogenous C16:0 palmitic fatty acid. In the normal state of insulin system and mitochondria, the frequent cause of insulin resistance is the non-optimal properties of dietary fatty acids supplied for oxidation by the mitochondria. Dietary excess of saturated palmitic fatty acid over monogenic oleic fatty acid causes insulin resistance to develop. Insulin resistance syndrome is the condition of in vivo energy deficiency and insufficient production of ATP for the realisation of the biological adaptation and compensation. Insulin effectively inhibits lipolysis only in phylogenetically late subcutaneous adipocytes but not in phylogenetically early visceral fat cells of the omentum. Discrepancy in the regulation of energy substrate metabolism against the background of a ‘relative biological perfection’ of higher mammals is the aetiological basis of insulin resistance.

Fat for fostering: Regenerating injured heart using local adipose tissue

Fat for fostering: Regenerating injured heart using local adipose tissue

Toona sinensis leaf extract inhibits lipid accumulation through up-regulation of genes involved in lipolysis and fatty acid oxidation in adipocytes.

Toona sinensis leaf (TSL) has been shown to lower plasma triacylglycerol levels and diminish the size of visceral fat cells in vivo. The molecular mechanism of TSL ethanol extract (TSL-E) on lipid metabolism in 3T3-L1 adipocytes was investigated in this study. Oil Red O staining as well as immunoblotting, real-time PCR, and dual-Luciferase reporter system were performed to investigate the effect of TSL-E on lipid accumulation and the regulation of lipid metabolism, respectively. In addition, active compounds in the TSL-E were analyzed by HPLC. TSL-E significantly decreased lipid accumulation, stimulated free fatty acid (FFA) release, and up-regulated peroxisome proliferator-activated receptor-α (PPARα) and genes involved in peroxisomal (acyl-CoA oxidase) and mitochondrial (uncouple protein 3) fatty acid oxidation. TSL-E also up-regulated cytoplasmic triacylglycerol hydrolysis gene (adipose triglyceride lipase) and genes related to fatty acid oxidation (AMP-activated protein kinase, acetyl-CoA carboxylase, carnitine palmitoyltransferase I, PPARγ, and adiponectin). The major constituents directly inducing PPARα transactivity in TSL-E are gallic acid, rutin, palmitic acid, linoleic acid, and α-linolenic acid. These results indicate that the inhibitory effect of TSL-E on lipid accumulation was through PPARα activation and further up-regulation of PPARα-mediated genes plus up-regulation of cytoplasmic genes involved in lipid catabolism.

Phylogenetically Theory of General Pathology. Nutritive Disturbance Is the Basis of Metabolic Syndrome Pathogenesis, Overeating Syndrome. Leptin and Adiponectin Role

Metabolic syndrome (overeating) is a phylogenetically-determined sequence of symptoms with the same pathogenesis. There is only one etiological factor, namely, increased consumption of physiologically optimal food. Enterocytes and omentum fat cells are phylogenetically paracrine-regulated cell community that realizes the biological reactions of exo- and endotrophy. Visceral obesity, high level of unesterified fatty acids (FA), formation of a pool of micellar FA in the blood, integration of these FA into endothelial cell plasma membrane and enlargement of adipocytes are the causes of hydrodynamic hypertension. Toll-like receptors recognize the albumin associates with greater amount of FA than physiologically required as non- self and initiate inflammatory process. Endoplasm stress forms in lipid-laden cells, protein synthesis (folding) impairs and induces apoptosis-like cell death. Visceral fat is a phylogenetically repository of FA to fulfill the biological function of homeostasis, trophology, endoecology and adaptation; it is regulated at the early level of paracrine communities and is anatomically limited. The subcutaneous fat repository fulfills the phylogenetically late function of locomotion; the repository size is not anatomically limited. Visceral fat cells don't have receptors for phylogenetically late insulin (INS); specialized adipoсytes laden with INS and GLUT4 receptors are cells that form the subcutaneous repository. These cells are regulated by phylogenetically late humoral factors at the body level. Leptin is the initiator of humoral hypothalamic regulation of in vivo sized ontogenetically programmed number of visceral INS-insensitive fat cells. It prevents endoplasm stress and apoptosis, being designed to regulate the amount of consumed food. Leptin initiates transformation of FA storing from visceral repository into subcutaneous repository. Adiponectin is phylogenetically late humoral hypothalamic regulatory factor that controls optimal number of fat cells in vivo. Its biological role is to regulate the number (proliferation) of insulin- dependent adipocytes in subcutaneous fatty tissue.

THU0259 The levels of adiponectin are decreased in the skin and sera of diffuse cutaneous systemic sclerosis patients

BackgroundAdiponectin is protein hormone produced by visceral and subcutaneous fat cells. In many past studies, adiponectin plays some roles in inflammation, angiogenesis and tissue remodeling, and induces the production of...

Beneficial effects of Chlorella on glucose and lipid metabolism in obese rodents on a high-fat diet

Obesity-induced glucose and lipid metabolism disorders have become risk factors for lifestyle diseases. Powderized Parachlorella beijerinckii (BP) and its hot water extract (BCEx) are believed to be useful for preventing common diseases such as hypertension, arteriosclerosis, and hyperlipidemia. The present study investigated how chlorella components influence common diseases in obese mice and rats on a high-fat diet. We fed C57BL/6J mice a high-fat diet containing 5% BP, and then weighed their organs, tested their glucose tolerance and insulin sensitivity, and analyzed their serum. Further, we fed Sprague-Dawley rats with a high-fat diet containing 1% BCEx, and then weighed their organs and analyzed their serum parameters. BP administration had no effect on high-fat diet-induced obesity. However, compared with high-fat diet group, BP group had improved glucose tolerance and insulin sensitivity and inhibited the hypertrophic growth of visceral fat cells. In addition, BP group had improved serum adiponectin, leptin and monocyte chemoattractant protein-1 (MCP-1) levels. The MCP-1 expression level at epididymal fat was decreased at BP group. BCEx administration reduced amount of peritesticular fat and serum triglyceride (TG) levels. The results suggest that the antihyperinsulinemic effects of BP are due to the modulation of adipose tissue hypertrophy and adipocytokine secretion. BCEx inhibited the accumulation of visceral fat and serum TG. The study showed that BP and BCEx improve glucose and lipid metabolism disorders caused by a high-fat diet.

Diet‐induced obesity has a differential effect on adipose tissue and macrophage inflammatory responses of young and old mice

Obesity and aging are both associated with increased inflammation in adipose tissue. In this study, we investigated effect of diet-induced obesity on inflammatory status in young and old mice. Young (2 months) and old (19 months) C57BL/6 mice were fed a low-fat (10%, LF) or high-fat (60%, HF) diet for 4.5 months. Adipose tissue from old/LF mice expressed higher levels of IL-1β, IL-6, TNFα, and cyclooxygenase-2 mRNA compared with young/LF mice. HF diet upregulated expression of all these inflammatory markers in young mice to the levels seen in the aged. Adipocytes, but not stromal vascular cells, from old/LF mice produced more IL-6, TNFα, and prostaglandin (PG)E2 than those from young/LF mice. HF diet resulted in an increase of all these markers produced by adipocytes in young, but only TNFα in old mice. PGE2 produced by peritoneal macrophages (Mϕ's) was upregulated with aging, and HF diet induced more IL-6, TNFα, and PGE2 production in young but not in old mice. Thus, HF diet/obesity induces an inflammatory state in both visceral fat cells and peritoneal Mϕ's of young mice, but not so in old mice. Together, these results suggest that HF diet-induced obesity may speed up the aging process as characterized by inflammatory status. This study also indicates that animals have a differential response, depending on their ages, to HF diet-induced obesity and inflammation. This age-related difference in response to HF diet should be considered when using inflammation status as a marker in investigating adverse health impacts of HF diet and obesity.

Okadaic Acid, a Bioactive Fatty Acid fromHalichondria okadai, Stimulates Lipolysis in Rat Adipocytes: The Pivotal Role of Perilipin Translocation

Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the black sponge Halichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes. However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin) remain unclear. We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release. Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis. Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment. Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor), calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis. These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.

Decreased adiponectin levels in the patients with diffuse cutaneous systemic sclerosis

Adiponectin is a protein hormone produced by visceral and subcutaneous fat cells. Adiponectin has been reported to play some roles in inflammation, angiogenesis and tissue remodeling, and induce the production of the anti-inflammatory mediators. Recently, adiponectin has also attracted attention for its involvement in the pathogenesis of collagen diseases. In this study, we determined the adiponectin expression in the sera and lesional skin of patients with systemic sclerosis (SSc). Serum adiponectin concentrations were measured in 32 patients with SSc, 10 patients with SLE, 12 patients with dermatomyositis and 13 normal subjects with specific enzyme-linked immunosorbent assays.

YC-1, a potent antithrombotic agent, induces lipolysis through the PKA pathway in rat visceral fat cells

This study investigated the effects of 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), a soluble guanylyl cyclase (sGC) activator and potential antithrombotic agent, on lipolysis in isolated visceral fat cells of the rat. Visceral fat cells were isolated from epididymal fat pads of rats and treated with YC-1 at different doses and times. Glycerol release, and intracellular cAMP and cGMP levels were analyzed by specific kits. Moreover, several inhibitors or drugs were used to examine the signal transduction pathways of YC-1-induced lipolysis in adipocytes. Herein we report that YC-1 stimulated glycerol release in dose- and time-dependent manners. Intracellular cAMP and cGMP levels of adipocytes both increased in time-dependent manners, but elevation of the cGMP level was faster and higher than that of the cAMP level after YC-1 treatment. An sGC inhibitor (ODQ) inhibited YC-1-induced glycerol release, indicating the involvement of sGC in YC-1-induced lipolysis. Administration of insulin, an activator of type-3B phosphodiesterase (PDE-3B), attenuated YC-1-induced lipolysis, indicating that elevation of the cAMP level is an important step in the lipolytic effect of YC-1. In addition, YC-1-induced lipolysis was inhibited by a protein kinase A (PKA) inhibitor (KT5720) but not by a PKG inhibitor (KT5823), indicating that YC-1-induced lipolysis occurs through a PKA-dependent pathway. A Western blot analysis showed that extracellular signal-regulated kinase was not phosphorylated by YC-1 treatment. In conclusion, our results suggest that YC-1 might stimulate lipolysis via activation of sGC/cGMP and then activation of the cAMP/PKA signaling cascade in isolated rat visceral adipocytes.