Adiponectin is an adipocyte-specific secretory hormone that can increase insulin sensitivity and promote adipocyte differentiation. Administration of adiponectin to obese or diabetic mice reduces plasma glucose and free fatty acid levels. Green tea polyphenols possess many pharmacological activities such as antioxidant, anti-inflammatory, antiobesity, and antidiabetic activities. To investigate whether green tea polyphenols have an effect on the regulation of adiponectin, we measured expression and secretion levels of adiponectin protein after treatment of each green tea polyphenols in 3T3-L1 adipocytes. We found that (−)-catechin enhanced the expression and secretion of adiponectin protein in a dose- and time-dependent manner. Furthermore, treatment of (−)-catechin increased insulin-dependent glucose uptake in differentiated adipocytes and augmented the expression of adipogenic marker genes, including PPARγ, CEBPα, FAS, and SCD-1, when (−)-catechin was treated during adipocyte differentiation. In search of the molecular mechanism responsible for inducible effect of (−)-catechin on adiponectin expression, we found that (−)-catechin markedly suppresses the expression of Kruppel-like factor 7 (KLF7) protein, which has recently been reported to inhibit the expression of adiponectin and other adipogenesis related genes, including leptin, PPARγ, C/EBPα, and aP2 in adipocytes. KLF7 is a transcription factor in adipocyte and plays an important role in the pathogenesis of type 2 diabetes. Taken together, these data suggest that the upregulation of adiponectin protein by (−)-catechin may involve, at least in part, suppression of KLF7 in 3T3-L1 cells.

Prp19p is an integral component of the heteromeric protein complex (the NineTeen complex) in the nucleus, and it is essential for the structural integrity of NineTeen complex and its subsequent activation of the spliceosome. We identified Prp19p, which has never been reported in relation to any function outside of the nucleus, as a member of proteins associated with lipid droplets. Down-regulation of Prp19p expression with RNA interference in 3T3-L1 cells repressed lipid droplet formation with the reduction in the level of expression of perilipin and S3-12. The levels of expression of SCD1 (stearoyl-CoA desaturase-1), DGAT-1 (acyl-CoA diacylglycerol acyltransferase-1), and glycerol-3-phosphate acyltransferase were also reduced in Prp19p down-regulated cells, and a significant decrease in triglycerides was observed. Unlike perilipin, which is one of the most extensively studied lipid droplet-associated proteins, Prp19p is not essential for cAMP-and hormone-sensitive lipasedependent lipolysis pathways, even though Prp19p is a component of the lipid droplet phospholipid monolayer, and downregulation of Prp19p represses fat accretion significantly. These results suggest that Prp19p or Prp19-interacting proteins during lipid droplet biogenesis in adipocytes may be considered as another class of potential targets for attacking obesity and obesity-related problems.Lipid droplets are subcellular organelles that function as major energy depots by storing neutral lipids, mainly triacylglycerols (1, 2). Therefore, the biogenesis of a lipid droplet is central to whole body energy homeostasis. In addition to their function as energy depots, lipid droplets appear to have important roles in lipid trafficking in adipocytes, cell signaling, and several important human diseases (3-7). It is thus important to understand the mechanism of deposition and mobilization of cellular neutral lipids. Although the mechanisms of lipid droplet biogenesis are still not entirely clear, it is expected that a set of proteins involved in lipid droplet biogenesis could comprise effective targets for the regulation of the whole body energy homeostasis. Lipid droplets are surrounded by a phospholipid monolayer into which many proteins are embedded (8). These surface proteins on adipocyte lipid droplets include structural proteins, such as PAT (perilripin/ADRP/TIP47) family proteins, S3-12, vimentin, and caveolin-1, and enzymes involved in many aspects of lipid metabolism, such as hormone-sensitive lipase (HSL)-, acyl-CoA synthetase-, lanosterol synthase-, CGI-58-, and NAD(P)-dependent steroid dehydrogenase-like protein and members of the Rab family of GTPases. Some of these lipid droplet-associated proteins are reported to play important roles in the functions of the lipid droplets (7, 9 -13).In this study, in order to explore proteins that are involved in lipid droplet biogenesis, we investigated the protein composition of lipid droplets isolated from cultured 3T3-L1 adipocytes, and we identified several more lipid droplet-associated proteins using ...

The regulation of adipocyte lipolysis is increasingly believed to influence insulin resistance, in a process that may be associated with mitochondrial dysfunction. However, the molecular basis of the relationship between mitochondrial protein expression, lipolytic responsiveness, and insulin resistance remains unknown. A set of proteins that shows altered abundances in the mitochondria of untreated and treated 3T3-L1 adipocytes with TNF-alpha or isoproterenol was identified. These include the proteins associated with energy production, including fatty acid oxidation, TCA cycle, and oxidative phosphorylation. Proteins associated with oxidative stress dissipation were down-regulated in lipolytically stimulated adipocytes. Lipolytic stimulation with isoproterenol and TNF-alpha, which is also a potent proinflammatory cytokine, showed some noticeable differences in mitochondrial protein expression. For example, isoproterenol markedly enhanced the expression of prohibitin which is involved in the integrity of mitochondria but TNF-alpha did not. These results provide valuable information on mitochondrial dysfunction associated with oxidative stress induced by lipolytic stimulation.

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK.

Fatigue is defined as difficulty in initiating or sustaining voluntary activity.1) Despite the prevalence of fatigue in developed countries, the pathophysiology and etiology of fatigue are unknown. Several underlying mechanisms of chronic fatigue syndrome (CFS) have been suggested: for example, allergic and psychological factors, 2) heavy exercise, viral infection, 3) muscle damage, 4,5) CNS disorders and immunological factors.6) Recent studies have demonstrated that energy metabolism is involved in the pathophysiology of fatigue. 7) At the biochemical level, fatigue is represented as the depletion of metabolic energy available to the cells that perform a myriad of functions vital to the survival of an organism.7) Metabolic energy is generated in the form of ATP through oxidative metabolism in the mitochondria. During energy generation, however, reactive oxygen species (ROS) are produced which have the potential to cause mitochondrial damage. The accumulation of mitochondrial dysfunction induced by ROS is proposed as "the mitochondrial theory of aging." 8) In addition, in CFS, impairment of mitochondrial function is frequently observed as represented by reduced oxidative metabolism, 9) increased anaerobic metabolism and subsequently increased lactate production.10,11) Mitochondrial abnormalities and degeneration are also frequently found in patients with CFS,12) reflecting the crucial role of mitochondria in the development of fatigue syndrome. In line with this, a wide variety of natural health products are used or are being developed to replenish the production of cellular energy in the mitochondria. 13)Chitooligosaccharides (COS) is an oligosaccharide made from chitin or chitosan by chemical or enzymatic decomposition.14,15) COS has attracted huge attention as a new biomedical material owing to its water-soluble character and versa- COS is also used as a health food for the treatment of fatigue. It has been suggested that the anti-fatigue effect of COS is related to its improvement of peripheral circulation, anti-oxidation, immunomodulation and nutritional effects. However, the exact mechanism underlying the anti-fatigue effect of COS remains to be elucidated. Sleep disturbance causes excessive energy consumption which leads to daytime fatigue and mental enervation. 26,27) Sleep deprivation increases the levels of the stress hormone cortisol, 28) and elevated cortisol levels induce the development of depression. 29) Researchers from the Karolinska Institute recently reported that decreased production of ATP in mitochondria may aggravate depressive disorders through the induction of high levels of somatization (physical symptoms). 30)In this study, we investigated the effect of COS in a sleep deprivation-induced fatigue model 31) in an effort to explore the utility of COS as a novel functional food with anti-fatigue effects, and examined its efficacy in terms of mitochondrial function and antioxidant activities. We discovered that COS lactate markedly decreased the severity of fatigue, as demonstrated by the d...