Mulberry (Morus alba) leaves are known to have therapeutic effects on lipid metabolism including lipogenesis, lipolysis and hyperlipidemia. However, novel compounds with strong lipolytic ability among 27 extracts of the mulberry leaves fermented with Cordyceps militaris (EMfCs) have not yet been identified. Therefore, the cAMP concentration and cell viability were measured in the primary adipocytes of SD (Sprague Dawley) rats and 3T3-L1 cells after treatment of 27 EMfCs. Briefly, mulberry leaves powders amended with three different concentrations (0, 25 and 50%) of silkworm pupae (SWP) powder were fermented with 10% C. militaris (v/w) during three different periods (3, 4 and 6 weeks). A total of 27 extracts were obtained from the fermented mulberry leaves powders using three different solvents (dH2O, 50% EtOH and 95% EtOH). Among the 27 EMfCs treated groups, a significant increase in the concentration of cAMP was detected in primary adipocytes treated with 10 extracts when compared with the Vehicle treated group. However, their cAMP concentration did not agree completely with the non-toxicity, although most extracts showed non-toxicity. Furthermore, the concentration of cAMP and level of free glycerol gradually increased in a dose dependent manner (100, 200 and 400 µg/mL) of 4M3-95 contained cordycepin without any significant toxicity. Overall, the results of this study provide strong evidence that 4M3-95 extract derived from EMfCs can stimulate the lipolysis of primary adipocytes at an appropriate concentration and therefore have the potential for use as lipolytic agents to treat obesity.
3T3-L1 Cells ; Adipocytes* ; Animals ; Bombyx ; Cell Survival ; Cordyceps* ; Glycerol ; Hyperlipidemias ; Lipid Metabolism ; Lipogenesis ; Lipolysis ; Morus* ; Obesity ; Powders ; Pupa ; Rats* ; Solvents ; Therapeutic Uses

OBJECTIVE: Catecholamine play a central role in the regulation of energy expenditure, in part by stimulating lipid mobilization through lipolysis in fat cells. The beta-2 adrenergic receptor(BAR-2) is a major lipolytic receptor in human fat cells. A recent study has shown that common polymorphisms occuring at codon 16 and 27 of the BAR-2 gene are significantly associated with obesity and lypolytic BAR-2 function in adipose tissue. We investigated whether the previously described human BAR-2 gene polymorphisms are associated with obesiy and NIDDM in Koreans. METHODS: All subjests were divided into two groups, non-obese and obese group, according to their body mass index. And their clinical characteristics were evaluated. The BAR-2 gene polymorphisms were analyzed by PCR-RFLP in 89 nondiabetics and 106 patients with NIDDM. RESULTS: When the allele frequency of BAR-2 gene polymorphisms was compared with that of western people, there was a significant difference. In our study, there was no significant difference in the allele frequency of BAR-2 gene polymorphisms at codons 16 and 27 between nonobese and obese group both nondiabetics and NIDDM subjects. The frequency of Glu27 homozygotes was very rare(1.1%). Body mass index(BMI), waist-hip ratio(WHR), and serum glucose and insulin secretion of the nondiabetics with polymorphism of codon 16 or codon 27 did not differ from those of the subjects without the polymorphisms. In NIDDM group, the Gly16 homozygotes had a lower BMI than Arg16 homozygotes without any difference in WHR and the other laboratory parameters. Neither clinical or laboratory parameters of the diabetics with the polymorphism at codon 27 differ from those of subjectes without the polymorphism. CONCLUSION: These findings suggest that the genetic variability in the human BAR-2 gene is not a major determinant for the development of obesity and NIDDM in Koreans.
Adipocytes ; Adipose Tissue ; Blood Glucose ; Body Mass Index ; Codon ; Diabetes Mellitus, Type 2 ; Energy Metabolism ; Gene Frequency ; Homozygote ; Humans ; Insulin ; Lipid Mobilization ; Lipolysis ; Obesity* ; Receptors, Adrenergic, beta-2*

Increased intracellular levels of Ca²⁺ are generally thought to negatively regulate lipolysis in mature adipocytes, whereas store-operated Ca²⁺ entry was recently reported to facilitate lipolysis and attenuate lipotoxicity by inducing lipophagy. Transient receptor potential mucolipin1 (TRPML1), a Ca²⁺-permeable non-selective cation channel, is mainly expressed on the lysosomal membrane and plays key roles in lysosomal homeostasis and membrane trafficking. However, the roles of TRPML1 in lipolysis remains unclear. In this study, we examined whether the channel function of TRPML1 induces lipolysis in mature adipocytes. We found that treatment of mature adipocytes with ML-SA1, a specific agonist of TRPML1, solely upregulated extracellular glycerol release, but not to the same extent as isoproterenol. In addition, knockdown of TRPML1 in mature adipocytes significantly reduced autophagic flux, regardless of ML-SA1 treatment. Our findings demonstrate that the channel function of TRPML1 partially contributes to lipid metabolism and autophagic membrane trafficking, suggesting that TRPML1, particularly the channel function of TRPML1, is as therapeutic target molecule for treating obesity.
Adipocytes ; Glycerol ; Homeostasis ; Isoproterenol ; Lipid Metabolism ; Lipolysis ; Membranes ; Obesity

Cancer cells rewire their metabolism to satisfy the demands of growth and survival, and this metabolic reprogramming has been recognized as an emerging hallmark of cancer. Lipid metabolism is pivotal in cellular process that converts nutrients into energy, building blocks for membrane biogenesis and the generation of signaling molecules. Accumulating evidence suggests that cancer cells show alterations in different aspects of lipid metabolism. The changes in lipid metabolism of cancer cells can affect numerous cellular processes, including cell growth, proliferation, differentiation, and survival. The potential dependence of cancer cells on the deregulated lipid metabolism suggests that enzymes and regulating factors involved in this process are promising targets for cancer treatment. In this review, we focus on the features associated with the lipid metabolic pathways in cancer, and highlight recent advances on the therapeutic targets of specific lipid metabolic enzymes or regulating factors and target-directed small molecules that can be potentially used as anticancer drugs.
Lipid Metabolism ; Lipogenesis ; Membranes ; Metabolic Networks and Pathways ; Metabolism

BACKGROUND/OBJECTIVES: Ginger, a root vegetable, is known to have antioxidant and antiobesity effects. Preparation, such as by steaming, can affect the chemical composition of prepared root vegetables or herbs and can change their functional activities. In the present study, we investigated the protective effects of steamed ginger against oxidative stress and steatosis in C57BL/6J mice fed a high-fat diet. MATERIALS/METHODS: The levels of polyphenols and flavonoids in two different extracts of steamed ginger, i.e., water extract (SGW) and ethanolic extract (SGE); as well, their antioxidant activities were examined. Forty male C57BL/6J mice were fed a normal diet (ND, n = 10), high-fat diet (HFD, 60% fat, w/w, n = 10), HFD supplemented with 200 mg/kg of SGE or garcinia (GAR) by weight (SGED or GARD, respectively, n = 10) for 12 weeks. Serum chemistry was examined, and the expressions of genes involved in lipid metabolism were determined in the liver. Histological analysis was performed to identify lipid accumulations in epididymal fat pads and liver. RESULTS: The SGE had higher contents of polyphenols and flavonoids and higher DPPH and ABTS⁺ free radical scavenging activities compared to those of SGW. Treatment with SGE or GAR significantly decreased the HFD-induced weight gain. Both SGE and GAR significantly reduced the high serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein levels induced by HFD. Compared to ND, HFD significantly increased hepatic TC and TG levels. SGE or GAR supplementation significantly decreased the increase of hepatic lipids by HFD. Interestingly, SGE had a more significant effect in reducing hepatic TC and TG levels than GAR. Furthermore, hepatic genes involved in lipogenesis and lipolysis were altered in both the SGED and GARD groups. CONCLUSIONS: The present study indicates that steamed ginger supplementation can decrease plasma TC and TG and can inhibit liver steatosis by regulating the expressions of hepatic genes.
Adipose Tissue ; Animals ; Chemistry ; Cholesterol ; Diet ; Diet, High-Fat* ; Ethanol ; Fatty Liver ; Flavonoids ; Garcinia ; Ginger* ; Humans ; Lipid Metabolism ; Lipogenesis ; Lipolysis ; Lipoproteins ; Liver ; Male ; Mice* ; Obesity* ; Oxidative Stress ; Plasma ; Polyphenols ; Steam* ; Triglycerides ; Vegetables ; Water ; Weight Gain

Adipose tissue is the main energy reserve of the body. When energy is required, adipocyte triglycerides stored in lipid droplets (LDs) are broken down by lipase, and free fatty acids are released to supply the physiological need. Intracellular LDs are active metabolic organelles in mammalian cells, particularly in adipocytes. The present study was aimed to investigate the morphological changes of LDs and the alternation of LD-associated perilipin family proteins during long-term lipolysis stimulated by forskolin. Primary differentiated adipocytes derived from epididymal fat pads of Sprague-Dawley (SD) rats were incubated in the presence or absence of 1 μmol/L forskolin for 24 h. Content of glycerol released to the culture medium was determined by a colorimetric assay and served as an index of lipolysis. Morphological changes of LDs were observed by Nile red staining. The mRNA level of perilipin family genes was detected by quantitative real-time PCR. The protein level and subcellular localization were examined by immunoblotting and immunofluorescence staining, respectively. The results showed that forskolin induced sustained lipolysis in differentiated adipocytes. The morphology of LDs changed in a time-dependent manner. Large clustered LDs became gradually smaller in size and eventually disappeared; in contrast, peripheral micro-LDs increased gradually in number until the cytoplasm was filled with numerous micro-LDs. The protein level of the perilipin family proteins showed obvious alternation. Mature adipocytes physiologically expressed a very low level of Plin2 protein, whereas in adipocytes stimulated with lipolytic forskolin, the protein and mRNA levels of Plin2 were significantly increased, and the increased Plin2 was specifically bound to the surface of LDs. During chronic stimulation of forskolin, the mRNA level of Plin3 was unchanged, but the mRNA levels of Plin1, Plin4 and Plin5 were significantly decreased. These results suggest that the morphology of LDs and perilipin family proteins on the surface of LDs are significantly altered during long-term lipolysis stimulated by forskolin, representing a dynamic process of the remodeling of LDs.
Adipocytes ; drug effects ; Animals ; Cells, Cultured ; Colforsin ; pharmacology ; Lipid Droplets ; Lipolysis ; Perilipin-2 ; metabolism ; Perilipins ; metabolism ; Rats ; Rats, Sprague-Dawley

The mechanistic target of rapamycin (mTOR) signaling pathway regulates many metabolic and physiological processes in different organs or tissues. Dysregulation of mTOR signaling has been implicated in many human diseases including obesity, diabetes, cancer, fatty liver diseases, and neuronal disorders. Here we review recent progress in understanding how mTORC1 (mTOR complex 1) signaling regulates lipid metabolism in the liver.
Animals ; Humans ; Lipid Metabolism ; Lipogenesis ; Liver ; cytology ; metabolism ; pathology ; Mechanistic Target of Rapamycin Complex 1 ; metabolism ; Signal Transduction

BACKGROUND/OBJECTIVES: Citrus flavonoids have a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated whether bioconversion of Citrus unshiu with cytolase (CU-C) ameliorates the anti-adipogenic effects by modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 cells. MATERIALS/METHODS: Glycoside forms of Citrus unshiu (CU) were converted into aglycoside forms with cytolase treatment. Cell viability of CU and CU-C was measured at various concentrations in 3T3L-1 cells. The anti-adipogenic and lipolytic effects were examined using Oil red O staining and free glycerol assay, respectively. We performed real time-polymerase chain reaction and western immunoblotting assay to detect mRNA and protein expression of adipogenic transcription factors, respectively. RESULTS: Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and instead, increased flavanone aglycoside forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with CU or CU-C at a dose of 0.5 mg/ml. Adipocyte differentiation was inhibited in CU-C group, but not in CU group. CU-C markedly suppressed the insulin-induced protein expression of CCAAT/enhancer-binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) as well as the mRNA levels of CEBPalpha, PPARgamma, and sterol regulatory element binding protein 1c (SREBP1c). Both CU and CU-C groups significantly increased the adipolytic activity with the higher release of free glycerol than those of control group in differentiated 3T3-L1 adipocytes. CU-C is particularly superior in suppression of adipogenesis, whereas CU-C has similar effect to CU on stimulation of lipolysis. CONCLUSIONS: These results suggest that bioconversion of Citrus unshiu peel extracts with cytolase enhances aglycoside flavonoids and improves the anti-adipogenic metabolism via both inhibition of key adipogenic transcription factors and induction of adipolytic activity.
3T3-L1 Cells* ; Adipocytes ; Adipogenesis ; Blotting, Western ; Cell Survival ; Citrus* ; Flavonoids ; Glycerol ; Lipid Metabolism ; Lipolysis ; Metabolism ; PPAR gamma ; RNA, Messenger ; Sterol Regulatory Element Binding Protein 1 ; Transcription Factors

PURPOSE:Growth hormone stimulates longitudinal growth, and it also exerts various effects on the metabolism of carbohydrates, lipids and proteins, indirectly regulating fuel metabolism. A hallmark is the stimulation of lipolysis, suppression of glucose oxidation, and development of insulin resistance. These metabolic effects subsequently affect body composition and atherogenic risk factors. There have recently been numerous reports concerning the metabolic effects of growth hormone, but the results are conflicting and exact cellular mechanism of action is yet unknown. The aim of this study is to assess the effect of biosythetic growth hormone replacement on carbohydrate and lipid metabolism and its subsequent effect on atherogenic risk in growth hormone deficient and idiopathic short stature. METHODS:We studied 111 idiopathic short stature patients and 12 children diagnosed with growth hormone deficiency by growth hormone provocation tests. Subjects were divided into three groups on the basis of duration of treatment; those who had been receiving GH replacement for 6, 12 and 18 months. Growth hormone was adminstered in a subcutaneous dose of 0.1 units per kg 6 times a week, and levels of blood sugar, total cholesterol, triglycerides, HDL-cholesterol, free fatty acid were measured before and after treatment in each group and changes in the atherogenic index (calculated as total cholesterol/HDL-cholesterol) were compared. RESULTS: 1)Blood sugar levels showed no significant change after GH therapy in both idiopathic short stature and growth hormone deficient groups. 2)Levels of total cholesterol showed a signficant decrease 6, 12 and 18 months after GH therapy in the idiopathic short stature patients, but no signficant change was noted in the growth hormone deficient patients. 3)GrowthhormonetherapyshowednosignificanteffectoneitherHDL-cholesterol or atherogenic index in both idiopathic short stature and growth-hormone deficient children. 4)There was no significant change in triglyceride and free fatty levels in children with idiopathic short stature after growth hormone therapy. CONCLUSIONS:Growth hormone administration significantly lowered total cholesterol levels in idiopathic short stature children, but failed to have a significant effect on atherogenic risk. Despite the increasingly widespread use of growth hormone in the treatment of hypopituitarism and non-GHD short stature, data concerning the metabolic effects of growth hormone are conflicting and the precise underlying mechanism is yet to be revealed, making further research necessary to determine the long term consequences of growth hormone replacement.
Blood Glucose ; Body Composition ; Carbohydrates ; Child ; Cholesterol ; Glucose ; Growth Hormone* ; Humans ; Hypopituitarism ; Insulin Resistance ; Lipid Metabolism* ; Lipolysis ; Metabolism ; Risk Factors ; Triglycerides

BACKGROUND/OBJECTIVES: Gelidium amansii (GA) contains plenty of agars and various biological substances, which make them a popular functional food to control body weight in previous studies. Unlike previous studies focused on agar in GA, objectives of this study were to investigate the effects of agar-free GA extract (AfGAE) on preventive and treatment models by using diets-induced obese (DIO) C57BL/6J mice. MATERIALS/METHODS: AfGAE were used to test their effects on the prevention (Exp-1) and treatment (Exp-2) against obesity after pilot study in DIO mice. The weight changes of the body and fat tissues and protein expression related to lipid metabolism and inflammation as well as plasma lipid profile and insulin were detected. RESULTS: Although AfGAE did not prevent long-term DIO, it did increase the levels of anti-inflammatory cytokine production and lipolysis protein. We further evaluated various doses of AfGAE in preventive and treatment models. As a result, our findings suggested that an AfGAE administration as a preventive model might be a better approach to achieve its anti-inflammatory and lipolysis-promoting effects in DIO mice. CONCLUSION: Although future studies to investigate the target materials such as polyphenols in AfGAE are required, the result suggests that GA without agar might be a therapeutic tool to improve health conditions related to inflammation.
Agar* ; Animals ; Body Weight ; Functional Food ; Inflammation ; Insulin ; Interleukin-10 ; Lipid Metabolism ; Lipolysis ; Mice ; Mice, Obese* ; Obesity ; Pilot Projects ; Plasma ; Polyphenols