Lipolysis In 3T3-L1 Cells Research Articles

Effects of Polygonatum sibiricum rhizome ethanol extract in high-fat diet-fed mice

Context: The rhizome of Polygonatum sibiricum Redoute (Liliaceae) has long been used to treat diabetes-associated complications. However, the pharmacological mechanism of P. sibiricum on metabolic disorders is not clear.Objective: This study investigates the effect of an ethanol extract of P. sibiricum rhizomes (designated ID1216) on obesity conditions including weight loss in high-fat (HF) diet-fed mice and explores the potential underlying mechanisms.Methods: To identify the metabolic impact of the P. sibiricum rhizome extract, HF diet-fed mice were administered ID1216 orally at doses of 250 and 1000 mg/kg/d for 10 weeks, and various factors related to metabolic syndrome were analyzed. We also examined the effects of ID1216 on the expression of genes involved in adipogenesis and lipolysis in 3T3-L1 cells, as well as genes associated with energy homeostasis in C2C12 myocytes.Results: ID1216 administration led to significant decreases in body weight gain (37.5%), lipid accumulation in adipose tissues (52.8%), and the levels of plasma triglycerides (26.4%) and free fatty acids (28.1%) at a dose of 250 mg/kg/d, compared with the vehicle-treated group, as well as improved insulin resistance. In addition, ID1216 was found to regulate the expression of genes related to adipogenesis and fatty acid oxidation in 3T3-L1 cells and enhance the expression of genes that modulate energy homeostasis in C2C12 myocytes.Conclusions: ID1216 may be a promising therapeutic agent for improving obesity conditions through the sirtuin-1 and peroxisome proliferator-activated receptor γ coactivator-1α pathway.

Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice

Fatty acid-binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. The aim of this study was to find new inhibitors of FABP4 for the treatment of type 2 diabetes. Human FABP4 protein was expressed, and its inhibitors were detected in 1,8-ANS displacement assay. The effect of the inhibitor on lipolysis activity was examined in mouse 3T3-L1 preadipocytes. The db/db mice were used to evaluate the anti-diabetic activity of the inhibitor. Molecular docking and site-directed mutagenesis studies were carried out to explore the binding mode between the inhibitor and FABP4. From 232 compounds tested, benzbromarone (BBR), an old uricosuric drug, was discovered to be the best inhibitor of FABP4 with an IC50 value of 14.8 μmol/L. Furthermore, BBR (25 μmol/L) significantly inhibited forskolin-stimulated lipolysis in 3T3-L1 cells. Oral administration of BBR (25 or 50 mg/kg, for 4 weeks) dose-dependently reduced the blood glucose level and improved glucose tolerance and insulin resistance in db/db mice. Molecular docking revealed that the residues Ser55, Asp76, and Arg126 of FABP4 formed important interactions with BBR, which was confirmed by site-directed mutagenesis studies. BBR is an inhibitor of FABP4 and a potential drug candidate for the treatment of type 2 diabetes and atherosclerosis.

Black soybean anthocyanins inhibit adipocyte differentiation in 3T3-L1 cells

Anthocyanins are naturally occurring polyphenolic pigments in plants that have been shown to decrease weight gain and insulin resistance in mice-fed high-fat diets. We investigated the effects of anthocyanins on cell growth, differentiation, and lipolysis in 3T3-L1 cells to test our hypothesis that anthocyanins could reduce adipose tissue mass by acting directly on adipocytes. Anthocyanin extracts from black soybeans were used and composed of 3 of the following major anthocyanins: cyanidine-3-O-glucoside (68.3%), delphinidin-3-O-glucoside (25.2%), and petunidin-3-O-glucoside (6.5%). Treatment with 12.5 and 50 μg/mL of black soybean anthocyanins exhibited inhibitory effects on the proliferation of both preconfluent preadipocytes (P < .01) and maturing postconfluent adipocytes (P < .01). In fully differentiated adipocytes, the number of viable cells was reduced by black soybean anthocyanins (P < .01). Treatment with 50 μg/mL of black soybean anthocyanins slightly increased epinephrine-induced lipolysis but decreased the basal lipolysis of fully differentiated adipocytes (P < .05). Black soybean anthocyanins also reduced lipid accumulation and suppressed the expression of the peroxisome proliferator–activated receptor γ, a major transcription factor for the adipogenic gene (P < .01). These results suggest that black soybean anthocyanins inhibit adipocyte differentiation and basal lipolysis, which may contribute to their antiobesity and antidiabetic properties.

Morus alba L. extracts inhibit adipocyte differentiation but stimulate lipolysis in 3T3-L1cells

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Cyclic phosphatidic acid influences the expression and regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 cells

Cyclic phosphatidic acid (cPA) is found in cells from slime mold to humans and has a largely unknown function. We previously reported that cPA significantly inhibited the lipid accumulation in 3T3-L1 adipocytes through inhibition of PPARγ activation. We find here that cPA reduced intracellular triglyceride levels and inhibited the phosphodiesterase 3B (PDE3B) expression in 3T3-L1 adipocytes. PPARγ activation in adipogenesis that can be blocked by treatment with cPA then participates in adipocyte function through inhibition of PDE3B expression. We also found the intracellular cAMP levels in 3T3-L1 adipocytes increased after exposure to cPA. These findings contribute to the participation of cPA on the lipolytic activity in 3T3-L1 adipocytes. Our studies imply that cPA might be a therapeutic compound in the treatment of obesity and obesity-related diseases.

Inhibition of Lipogenesis and Stimulation of Lipolysis in 3T3 L1 Cells by a Garcinia Extract

Inhibition of Lipogenesis and Stimulation of Lipolysis in 3T3 L1 Cells by a Garcinia Extract

Grain of paradise extracts increase energy expenditure in humans

ObjectiveGrain of paradise (GP; Aframomum melegueta) is an herbaceous plant from the ginger family. Two components of GP, paradol and gingerol, are structurally similar to capsaicin, a pungent compound with anti‐obese actions. Our group investigated the effects of GP‐extracts on energy expenditure and the prevention of obesity.MethodsWe investigated the effects of GP‐extracts on norepinephrine (NE)‐induced lipolysis in 3T3‐L1 cells, on the progression of obesity in high fat diet (HFD)‐induced obese mice, and on body weight and energy expenditure in humans receiving repeated doses of the extracts for 4 weeks.ResultsGP‐extracts accelerated lipolysis in 3T3‐L1 cells. In the obese mice, the extracts prevented HFD‐induced elevations in body and adipose tissue weights. In humans, the energy expenditure observed after the intake of GP‐extracts differed significantly from that observed before the intake.ConclusionGP‐extracts intake enhances the energy expenditure and basal metabolism in humans, possibly via an acceleration of lipolysis followed by fat combustion. The effects of GP‐extracts on energy expenditure are thought to be caused by paradol and gingerol major components of the extract.

CGI-58 facilitates lipolysis on lipid droplets but is not involved in the vesiculation of lipid droplets caused by hormonal stimulation

A lipid droplet (LD)-associated protein, perilipin, is a critical regulator of lipolysis in adipocytes. We previously showed that Comparative Gene Identification-58 (CGI-58), a product of the causal gene of Chanarin-Dorfman syndrome, interacts with perilipin on LDs. In this study, we investigated the function of CGI-58 using RNA interference. Notably, CGI-58 knockdown caused an abnormal accumulation of LDs in both 3T3-L1 preadipocytes and Hepa1 hepatoma cells. CGI-58 knockdown did not influence the differentiation of 3T3-L1 adipocytes but reduced the activity of both basal and cAMP-dependent protein kinase-stimulated lipolysis. In vitro studies showed that CGI-58 itself does not have lipase/esterase activity, but it enhanced the activity of adipose triglyceride lipase. Upon lipolytic stimulation, endogenous CGI-58 was rapidly dispersed from LDs into the cytosol along with small particulate structures. This shift in localization depends on the phosphorylation of perilipin, because phosphorylated perilipin lost the ability to bind CGI-58. During lipolytic activation, LDs in adipocytes vesiculate into micro-LDs. Using coherent anti-Stokes Raman scattering microscopy, we pursued the formation of micro-LDs in single cells, which seemed to occur in cytoplasmic regions distant from the large central LDs. CGI-58 is not required for this process. Thus, CGI-58 facilitates lipolysis in cooperation with perilipin and other factors, including lipases.

Effect of tea catechins on intracellular lipolysis in 3T3-L1 cells.

Effect of tea catechins on intracellular lipolysis in 3T3-L1 cells.

Pycnogenol stimulates lipolysis in 3t3‐L1 cells via stimulation of β‐receptor mediated activity

The influence of pycnogenol on the glycerol released into the medium in fully differentiated 3T3-L1 cells was studied. After incubation for 2 h, pycnogenol stimulated glycerol release in a dose-dependent manner. Pretreatment with the beta-receptor antagonist, propranolol, significantly reduced pycnogenol-induced lipolysis in a dose-dependent manner. When fully differentiated 3T3-L1 cells were incubated with pycnogenol, the cyclic adenosine monophosphate content significantly increased. These data suggested that pycnogenol has strong lipolytic effects via stimulation of beta-receptor mediated activity.

Stimulation of lipolysis by pycnogenol.

We studied the influence of pycnogenol on the lipolysis of 3T3 L1 cells after differentiation. When pycnogenol or epinephrine was exposed to mature adipocytes, the smaller (less than 20 microm(2)) intracytoplasmic lipid droplets selectively disappeared. These data suggest that pycnogenol stimulates lipolysis.

３Ｔ３‐Ｌ１脂肪細胞を用いての脂肪分解促進作用を持つ植物エキスの検索

３Ｔ３‐Ｌ１脂肪細胞を用いての脂肪分解促進作用を持つ植物エキスの検索

Cachectin/tumor necrosis factor and interleukin-1 show different modes of combined effect on lipoprotein lipase activity and intracellular lipolysis in 3T3-L1 cells

Cachectin/tumor necrosis factor (cachectin/TNF) and interleukin-1 (IL-1) share many effects in various tissues and cells, including suppression of lipoprotein lipase (LPL) activity and enhancement of intracellular lipolysis. A possible interaction between cachectin/TNF and IL-1 in these lipase systems was studied in 3T3-L1 adipocytes. The two cytokines showed marked synergy in their suppression of LPL activity in these adipocytes. The least effective dose of cachectin/TNF or IL-1 was at around 5 x 10(-11) or 2.5 x 10(-12) M, respectively. However, when present in combination in amounts as small as 1/20 or 1/100 of the minimum effective dose for either cytokine alone (2.5 x 10(-12) M cachectin/TNF and 2.5 x 10(-14) M IL-1), the cytokines showed marked suppression of LPL activity. In marked contrast, such synergism was not seen for enhancement of intracellular lipolysis. This discrepancy in the combined effects of the two monokines on the two different enzyme systems in the same cells suggests that synergism between cachectin/TNF and IL-1 is unlikely at the level of their receptors on the surface of 3T3-L1 cells. Because the two monokines are considered to be secreted from macrophages under similar conditions, their effect on LPL suppression in many pathophysiological situations would be much greater than that of either monokine alone.

Effect of epinephrine and other lipolytic agents on intracellular lipolysis and lipoprotein lipase activity in 3T3-L1 adipocytes.

3T3-L1 adipocytes were used to test the hypothesis that hormone-sensitive lipolysis and lipoprotein lipase activity might be regulated in a reciprocal manner. Intracellular lipolysis was stimulated by catecholamine, dibutyryl cAMP, and ACTH, but not by glucagon. The effects of epinephrine on lipolysis were blocked by the beta-antagonist propanolol but not by the alpha-antagonist phentolamine. Hormone-stimulated lipolysis was not changed by acute (45 min) or chronic (2 days) treatment of the cells with insulin whereas the latter treatment augmented lipoprotein lipase activity about fivefold. Epinephrine did not affect the lipoprotein lipase activity of insulin-stimulated cells. Withdrawal of glucose from the medium decreased lipoprotein lipase activity and the effect of epinephrine on lipolysis. Effects of lipolytic agents on activity of lipoprotein lipase were variable and concentration-dependent. Lipoprotein lipase activity was decreased only by concentrations of epinephrine greater than those inducing maximal intracellular lipolysis, and the decrease in activity occurred about 30 min after the increase in glycerol release. There seems to be no relationship between the level of activity of lipoprotein lipase and the maximal rate of hormone-stimulated lipolysis in 3T3-L1 cells. Unlike in adipose tissue and adipocytes of rats, hormone-stimulated lipolysis and lipoprotein lipase activity in murine 3T3-L1 adipocytes appear to be regulated independently.