Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction.

BACKGROUND: Kisspeptin is the leading upstream regulator of pulsatile and surge Gonadotrophin-Releasing Hormone secretion (GnRH) in the hypothalamus, which acts as the key governor of the hypothalamic-pituitary-ovary axis. MAIN TEXT: Exogenous kisspeptin or its receptor agonist can stimulate GnRH release and subsequent physiological gonadotropin secretion in humans. Based on the role of kisspeptin in the hypothalamus, a broad application of kisspeptin and its receptor agonist has been recently uncovered in humans, including central control of ovulation, oocyte maturation (particularly in women at a high risk of ovarian hyperstimulation syndrome), test for GnRH neuronal function, and gatekeepers of puberty onset. In addition, the kisspeptin analogs, such as TAK-448, showed promising agonistic activity in healthy women as well as in women with hypothalamic amenorrhoea or polycystic ovary syndrome. CONCLUSION: More clinical trials should focus on the therapeutic effect of kisspeptin, its receptor agonist and antagonist in women with reproductive disorders, such as hypothalamic amenorrhoea, polycystic ovary syndrome, and endometriosis.

Preparation, evaluation, and in vitro cytotoxicity studies of artesunate-loaded glycyrrhetinic acid decorated PEG-PLGA nanoparticles.

OBJECTIVE: The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity. SIGNIFICANCE: The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug. METHODS: The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition, physical properties were determined, including particle size, polydispersity index (PDI), zeta potential (ZP), morphology, drug loading capacity (LC) and encapsulation efficiency (EE), and in vitro drug release. Moreover, the in vitro cytotoxicity of NPs with three human cancer cell lines viz. HepG2, Hep3B, and SMCC-7721 was conducted using the SRB assay. Additionally, lyophilization was conducted to improve the long-term physical stability. RESULTS: The GA-PEG-PLGA-ART NPs have spherical shape, small particle size (around 88 nm) with a narrow size distribution (PDI < 0.3), high drug LC (up to 59.3 ± 1.65%), and high EE (up to 73.13 ± 5.17%). In vitro drug release behavior showed that drugs were released from NPs in a sustained and controlled release pattern. Cytotoxicity study indicated the NPs achieved lower cancer cell survival fraction. The GA-PEG-PLGA NPs freeze-dried with 3% (w/v) of mannitol showed better effect on long-term physical stability. CONCLUSION: The GA-PEG-PLGA-ART NPs appear as a potential liver targeted intracellular delivery platform for ART.

Predicted secreted protein analysis reveals synaptogenic function of Clstn3 during WAT browning and BAT activation in mice.

Promoting white adipose tissue (WAT) browning and enhancing brown adipose tissue (BAT) activity are attractive therapeutic strategies for obesity and its metabolic complications. Targeting sympathetic innervation in WAT and BAT represents a promising therapeutic concept. However, there are few reports on extracellular microenvironment remodeling, especially changes in nerve terminal connections. Identifying the key molecules mediating the neuro-adipose synaptic junctions is a key point. In this study, we used bioinformatics methods to identify the differentially expressed predicted secreted genes (DEPSGs) during WAT browning and BAT activation. These DEPSGs largely reflect changes of cytokines, extracellular matrix remodeling, vascularization, and adipocyte-neuronal cross-talk. We then performed functional enrichment and cellular distribution specificity analyses. The upregulated and downregulated DEPDGs during WAT browning displayed a distinctive biological pattern and cellular distribution. We listed a cluster of adipocyte-enriched DEPSGs, which might participate in the cross-talk between mature adipocytes and other cells; then identified a synaptogenic adhesion molecule, Clstn3, as the top gene expressed enriched in both mature white and brown adipocytes. Using Q-PCR and immunohistochemistry, we found significantly increased Clstn3 expression level during WAT browning and BAT activation in mice subjected to cold exposure (4 °C). We further demonstrated that treatment with isoproterenol significantly increased Clstn3 and UCP1 expression in differentiated white and beige adipocytes in vitro. In conclusion, our study demonstrates that the secretion pattern was somewhat different between WAT browning and BAT activation. We reveal that Clstn3 may be a key gene mediating the neuro-adipose junction formation or remodeling in WAT browning and BAT activation process.

A novel role for Bcl2l13 in promoting beige adipocyte biogenesis.

Bcl2l13 is a member of the Bcl-2 family that has been found to play a central role in regulating apoptosis. Recently Bcl2l13 has been reported to induce mitophagy as a functional mammalian homolog of Atg32. However, the role of Bcl2l13 in adipose tissue has not been investigated yet. In the present study, we found that Bcl2l13 expression was increased in white adipose tissue browning process stimulated by cold exposure or ß3-adrenergic agonist CL-316,243 in vivo as well as during brown adipocytes differentiation in vitro. Moreover, Bcl2l13 disruption dramatically inhibited the browning program of preadipocytes, evidenced by reduced Prdm16, Ucp1, Dio2 and Adrb3 expression. Our findings revealed that the inhibition effect of Bcl2l13 disruption on browning program may be independent of altering autophagy activity, but through regulating mitochondrial dynamic and biogenesis, supported by decreased mitochondrial fission/fussion genes, PGC-1α and mitochondrial respiratory chain complexes expression. Taken together, our study uncovered a novel function of Bcl2l13 in adipocytes differentiation and promoting browning program.

Liraglutide ameliorates non-alcoholic fatty liver disease by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a pathway.

AIM: Overwhelming oxidative stress is implicated as crucial in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Liraglutide, a well-established antidiabetes drug, was recently reported to ameliorate NAFLD with an elusive mechanism. We used a mouse model to examine whether liraglutide could ameliorate NAFLD and explored the possible mechanisms. METHODS: Twenty C57BL/6J mice were randomly treated with a normal-fat diet or high-fat diet for 16 weeks, then further distributed into four groups and subjected to s.c. injection of liraglutide or saline for 4 weeks. The growth/metabolism, oxidative stress, mitochondrial architecture and autophagy were assessed prospectively at the 20th week. RESULTS: High-fat diet inducement resulted in severe NAFLD while liraglutide treatment significantly reversed the trend, marked by reduced bodyweight, improved glucose tolerance and liver triglyceride composition. Reduced hepatic malondialdehyde level, increased mRNA and protein levels of CATALASE and MNSOD indicated liraglutide affected both the oxidative and antioxidative process to ameliorate oxidative stress. After liraglutide administration, the upregulated mRNA and protein levels of mitochondrial fission and fusion-related DRP1, OPA1 and respiratory chain-related COMPLEX1, UCP2 demonstrated the enhancement of mitochondrial architecture which may attenuate the generation of reactive oxygen species (ROS), while the diminished mRNA and protein level of P62 and increased levels of Beclin1 and LC3II/I ratio indicated the promoting autophagy, which probably contribute to the ROS elimination. Further, restored protein levels of Sirtuin1/Sirtuin3 and the downstream p-FOXO3a reveal the probable pathways of liraglutide acting on autophagy. CONCLUSION: Liraglutide diminishes oxidative stress by enhancing mitochondrial architecture and promoting autophagy through the SIRT1/SIRT3-FOXO3a-LC3 pathway to ameliorate diet-induced NAFLD.

Endurance exercise ameliorates low birthweight developed catch-up growth related metabolic dysfunctions in a mouse model.

Low birthweight is known to predict high risk of metabolic diseases in adulthood, while regular endurance exercises are believed sufficient to improve metabolic dysfunction. In this study, we established a mouse model to determine whether long-term exercise training could ameliorate catch-up growth, and we explored the possible underlying mechanisms. By restricting maternal food intake during the last week of gestation, we successfully produced low birthweight pups. Further, normal birthweight mice and low birthweight mice were randomly distributed into one of three groups receiving either a normal fat diet, high fat diet, or high fat diet with exercise training. The growth/metabolism, mitochondrial content and functions were assessed at 6 months of age. Through group comparisons and correlation analyses, the 4th week was demonstrated to be the period of crucial growth and chosen to be the precise point of intervention, as the growth rate at this point is significantly correlated with body weight, intraperitoneal glucose tolerance test (IPGTT), Lee's index and fat mass in adulthood. In addition, regular endurance exercises when started from 4 weeks remarkably ameliorated low birthweight outcomes and induced catch-up growth and glucose intolerance in the 25th week. Furthermore, real-time PCR and western blot results indicated that the effect of long-term exercise on mitochondrial functions alleviated catch-up related metabolic dysfunction. To conclude, long-term exercise training from the 4th week is sufficient to ameliorate catch-up growth and related metabolic disturbances in adulthood by promoting mitochondrial functions in skeletal muscle.

Comparative chemical profiling of leaf essential oils from Cinnamomum kanehirae and related species using steam distillation and solvent extraction: Implications for plant-based classification.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

Microsatellite primers for the endangered beech tree, Fagus hayatae (Fagaceae).

PREMISE OF THE STUDY: Microsatellite primers were developed for the endangered species Fagus hayatae (Fagaceae) to investigate the genetic diversity of the population and to investigate species delimitation within Fagus. METHODS AND RESULTS: Ten polymorphic simple sequence repeat markers were developed for F. hayatae using a magnetic bead enrichment method. The primers amplified trinucleotides, hexanucleotides, and complex repeats with six to 16 alleles per locus. The observed and expected heterozygosities across loci varied, with a range of 0.05-0.71 and 0.63-0.91, respectively. Most of the primers also amplified DNA from F. crenata, F. grandifolia, F. japonica, F. longipetiolata, F. lucida, F. orientalis, and F. sylvatica. CONCLUSIONS: These results indicate that these polymorphic loci of F. hayatae will be potentially useful for future studies of the population genetic diversity within the species. In addition, the interspecific amplification indicates that these transferable microsatellite markers will also be useful for future phylogeographic and speciation studies among close Fagus species.

Characterization of microsatellite loci from Litsea hypophaea (Lauraceae), a tree endemic to Taiwan.

PREMISE OF THE STUDY: Microsatellite primers were developed for the endemic tree Litsea hypophaea (Lauraceae) in Taiwan to investigate its genetic diversity and population genetic structure and to investigate species delimitation within Litsea. METHODS AND RESULTS: Fifteen new simple sequence repeat markers were developed from L. hypophaea with a magnetic bead enrichment method. Most loci were also amplified from three closely related species, L. coreana, L. lii, and L. acutivena. The number of alleles and observed and expected heterozygosities across loci varied with a range of 1-25, 0.000-1.000, and 0.000-0.956, respectively. CONCLUSIONS: The application of these microsatellite markers of L. hypophaea provides a tool for understanding genetic diversity and population differentiation. In addition, interspecific amplification suggests that these markers will also be useful for species identification of related taxa within Litsea in Taiwan.

Diagnostic Value of Kisspeptin Levels on Early Pregnancy Outcome: a Systematic Review and Meta-analysis.

The objective of this study is to investigate whether kisspeptin levels in early pregnancy have a better diagnostic value on early pregnancy outcome as compared with human chorionic gonadotropin (hCG). This study was a systematic review and meta-analysis aiming to investigate the diagnostic value of kisspeptin levels on early pregnancy outcome. The primary outcome was miscarriage or viable intrauterine pregnancy. Five studies were included for systematic review, and three studies were included for meta-analysis. Meta-analysis showed kisspeptin levels had a good diagnostic value with the area under the curve (AUC) 0.902 (0.866, 0.937) when kisspeptin was measured after 6 weeks of gestation. Sensitivity analysis demonstrated kisspeptin levels had a diagnostic value with AUC = 0.881 (0.855, 0.906). hCG levels had a diagnostic value with AUC = 0.834 (0.785, 0.883), which was inferior to the diagnostic value of kisspeptin (mean difference = 0.09 (0.02, 0.16)). Kisspeptin measurement has a potential for comparable or even higher accuracy than hCG in differentiating between miscarriage and viable intrauterine pregnancy after 6 weeks of gestation.

Structured Populations of Critically Endangered Yellow Water Lily (Nuphar shimadai Hayata, Nymphaeaceae).

Yellow water lily (Nuphar shimadai Hayata) is a critically endangered species in Taiwan. Here, we examined genetic structures of four extant populations, WP, GPa, GPb and GPn, using 39 simple sequence repeat (SSR) markers. Positive genetic correlation was observed within 50 m, beyond which no correlation was detected due to isolation by distance according to Mantel correlogram. This suggests a significant genetic structuring of the species. Besides, multilocus genotype (MLG) analysis revealed that GPa was a panmictic population and the species' putative center of origin. Genetic exchange was observed between GPa and GPb populations, which likely resulted from their geographic proximity. Nevertheless, there was a strong asymmetric migration detected from GPa to WP, but a recent genetic barrier prevented dispersal further northward (WP). Geneland estimated the best number of clusters as K = 2, where WP distinctly separated from the rest of the populations. In STRUCTURE output of K = 3, a third cluster was abundant only in WP. We suggest to consider GPn and WP as separate conservation units, being far from GPa. There is indeed a need to investigate these populations; as predicted, Ne = 1.6 to 3.0 is considered low and that may put the species at risk of extinction.

Microsatellite primers in the native perennial cycad Cycas taitungensis (Cycadaceae).

PREMISE OF THE STUDY: Microsatellite primers were developed for the native perennial cycad Cycas taitungensis to evaluate the genetic variation of this endangered insular species. METHODS AND RESULTS: Using a magnetic bead enrichment method and EST data, 16 primer sets were developed and identified for the native Taiwan cycad C. taitungensis. The primers amplified dinucleotide, trinucleotide, and complex repeats with 1-9 alleles per locus. Most primers also amplified DNA from C. revoluta and C. debaoensis. CONCLUSIONS: These results indicate the utility of primers for future studies of the genetic structure of C. taitungensis. In addition, the primers are useful for further phylogeographic studies between C. taitungensis and C. revoluta, which is a closely related species.

Isolation of 16 polymorphic microsatellite markers from an endangered and endemic species, Podocarpus nakaii (Podocarpaceae).

PREMISE OF THE STUDY: Sixteen polymorphic microsatellite markers were isolated and characterized from the endangered evergreen tree Podocarpus nakaii to evaluate the population structure for conservation efforts. METHODS AND RESULTS: Based on a modified amplified fragment length polymorphism and magnetic bead enrichment method, 16 polymorphic primer sets were developed for this endangered insular species. Allele numbers ranged from five to seven, with an observed heterozygosity ranging from 0.29 to 0.88. Most primers were able to amplify DNA from the endemic P. fasciculus and the widely distributed P. macrophyllus var. macrophyllus, P. macrophyllus var. maki, and P. costalis. CONCLUSIONS: The results reported here indicate the usefulness of codominant markers for future studies of the population genetics of P. nakaii. In addition, the markers are useful for further phytogeographic and speciation studies in P. fasciculus, P. macrophyllus var. macrophyllus, and P. macrophyllus var. maki, which are closely related species.

Nonalcoholic Fatty Liver Disease: Pathogenesis and Treatment in Traditional Chinese Medicine and Western Medicine.

Nonalcoholic Fatty Liver Disease (NAFLD) is one of the most important causes of liver disease worldwide and probably destined to become the leading cause of end-stage liver disease in the coming decades, affecting both adults and children. Faced with the severe challenges for the prevention and control of NAFLD, this article discusses the understanding and mechanism of NAFLD from Chinese and Western medicine. Moreover, the progress regarding its treatment in both Chinese and Western medicine is also summarized. Both Chinese medicine and Western medicine have their own characteristics and clinical efficacy advantages in treating diseases. The purpose of this article is to hope that Chinese and Western medicine have complementary advantages, complementing each other to improve clinical NAFLD therapy prevention and treatment methods to receive more and more attention throughout the global medical community.

Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway.

Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.

Global dynamics and transition state theories: Comparative study of reaction rate constants for gas-phase chemical reactions.

In this review article, we present a systematic comparison of the theoretical rate constants for a range of bimolecular reactions that are calculated by using three different classes of theoretical methods: quantum dynamics (QD), quasi-classical trajectory (QCT), and transition state theory (TST) approaches. The study shows that the difference of rate constants between TST results and those of the global dynamics methods (QD and QCT) are seen to be related to a number of factors including the number of degrees-of-freedom (DOF), the density of states at transition state (TS), etc. For reactions with more DOF and higher density of states at the TS, it is found that the rate constants from TST calculations are systematically higher than those obtained from global dynamics calculations, indicating large recrossing effect for these systems. The physical insight of this phenomenon is elucidated in the present review.

Obesity-associated inflammation triggers an autophagy-lysosomal response in adipocytes and causes degradation of perilipin 1.

In obesity, adipocytes exhibit high metabolic activity accompanied by an increase in lipid mobilization. Recent findings indicate that autophagy plays an important role in metabolic homeostasis. However, the role of this process in adipocytes remains controversial. Therefore, we performed an overall analysis of the expression profiles of 322 lysosomal/autophagic genes in the omental adipose tissue of lean and obese individuals, and found that among 35 significantly differentially expressed genes, 34 genes were upregulated. A large number of lysosomal/autophagic genes also were upregulated in murine 3T3-L1 adipocytes challenged with tumor necrosis factor α (TNFα) (within 24 h), which is in accordance with increased autophagy flux in adipocytes. SQSTM1/p62, a selective autophagy receptor that recognizes and binds specifically to ubiquitinated proteins, is transcriptionally upregulated upon TNFα stimulation as well. Perilipin 1 (PLIN1), a crucial lipid droplet protein, can be ubiquitinated and interacts with SQSTM1 directly. Thus, TNFα-induced autophagy is a more selective process that signals through SQSTM1 and can selectively degrade PLIN1. Our study indicates that local proinflammatory cytokines in obese adipose tissue impair triglyceride storage via autophagy induction.

Nuclear and chloroplast DNA phylogeography suggests an Early Miocene southward expansion of Lithocarpus (Fagaceae) on the Asian continent and islands.

BACKGROUND: Most genera of Fagaceae are thought to have originated in the temperate regions except for the genus Lithocarpus, the stone oaks. Lithocarpus is distributed in subtropical and tropical Asia, and its ancestral population is hypothesized to be distributed in tropical regions in Borneo and Indochina. Borneo and the nearby islands (the Greater Sunda Islands) were connected to the Malay Peninsula and Indochina prior to the Pliocene epoch and formed the former Sundaland continent. The Southeast Asian Lithocarpus, is thought to have dispersed between continental Asia and the present Sundaland. The drastic climate changes during the Pliocene and Pleistocene epochs which caused periodic sea-level changes is often used to explain the cause of its diversity. The aim of this study was to establish phylogenetic relationships by analyzing nuclear (nrDNA) and chloroplast (cpDNA) DNA in order to describe and analyze the origin, causes of diversification and historical biogeography of Lithocarpus. RESULTS: Phylogeny reconstructed through the multiple-species coalescent method with nrDNA and cpDNA revealed that the continental-Asian taxa were clustered at the basal lineages. The derived lineages of tropical Lithocarpus, with the inference of a subtropical ancestral state, imply a southward migration in the Early Miocene period with subsequent in situ diversification in the Greater Sunda Islands. The gradual decrease in temperature since the Middle Miocene period is proposed as a cause of the increase in the net diversification rate. CONCLUSIONS: The historical ancestral origin of Lithocarpus has been suggested to be mainland Asia. Southward migration in the Early Miocene period with subsequent in situ diversification could explain the current diversity of stone oaks in Southeast Asia. This study also considered the multiple origins of stone oaks currently indigenous to the subtropical islands offshore and near mainland China. Our results provide phylogenetic evidence for a subtropical origin of Asian stone oaks and reveal the process of diversification and how it fits into the timeline of major geologic and climatic events rather than local, episodic, rate-shifting events.

Characterization of 39 microsatellite markers from Nuphar shimadai (Nymphaeaceae) and cross-amplification in two related taxa.

PREMISE OF THE STUDY: Microsatellite loci were developed for Nuphar shimadai (Nymphaeaceae) to evaluate the population genetic dynamics for conservation purposes. The species is an endemic aquatic species in Taiwan that is endangered by anthropogenic activities. METHODS AND RESULTS: A magnetic bead enrichment protocol was used to identify 72 potential microsatellite loci and develop 39 microsatellite markers from N. shimadai. The number of alleles per locus ranged from one to 10 per locus, with levels of observed heterozygosity ranging from 0 to 1.0 within populations. As a result of inbreeding within isolated populations, 65% of loci significantly deviated from Hardy-Weinberg equilibrium within populations. CONCLUSIONS: These novel markers should be valuable tools to evaluate the genetic diversity within the endangered aquatic taxon N. shimadai for conservation and reintroduction purposes in Taiwan.

Antioxidant MMCC ameliorates catch-up growth related metabolic dysfunction.

Postnatal catch-up growth may be related to reduce mitochondrial content and oxidation capacity in skeletal muscle. The aim of this study is to explore the effect and mechanism of antioxidant MitoQuinone mesylate beta cyclodextrin complex (MMCC) ameliorates catch-up growth related metabolic disorders. Catch-up growth mice were created by restricting maternal food intake during the last week of gestation and providing high fat diet after weaning. Low birthweight mice and normal birthweight controls were randomly subjected to normal fat diet, high fat diet and high fat diet with MMCC drinking from the 4th week. MMCC treatment for 21 weeks slowed down the catch up growth and ameliorated catch-up growth related obesity, glucose intolerance and insulin resistance. MMCC administration significantly inhibited the peroxidation of the membrane lipid and up-regulated the antioxidant enzymes Catalase and MnSOD. In addition, MMCC treatment effectively enhanced mitochondrial functions in skeletal muscle through the up-regulation of the ATP generation, and the promotion of mitochondrial replication and remodeling. To conclude, this study demonstrates that antioxidant MMCC effectively ameliorates catch-up growth related metabolic dysfunctions by increasing mitochondrial functions in skeletal muscle.