Objective: To explore the effect and mechanism of omega 3-polyunsaturated fatty acid(ω3-PUFA) dietary intervention on mitochondrial function of white adipose tissue in adult rats with postnatal early overfeeding. Methods: An overfed animal model by adjusting litter size was developed for the study of neonatal overfeeding. The litter size was adjusted to 3 male rats per litter(small litter, SL group) and 10 pups per litter(normal litter, NL group). After weaning(week 3), the pups were fed standard chow or ω3-PUFA diet(SL-FO) until postnatal weeks 13. Food intake, body weight, and rectal temperature of rats were measured regularly, and energy metabolism of animals was monitored in week 13. During week 3 and 13, subcutaneous adipose tissue was collected. Inguinal preadipocytes of mice were isolated and induced to differentiate, and 50 μmol/L eicosapentaenoicacid(EPA) was administered for 48 h at the late stage of differentiation. The mRNA and protein expression levels of mitochondrial related genes, mitochondrial copy number, and oxygen consumption rate of adipocytes were detected in adipose tissue and adipocytes. Results: By the 3rd week, the body weight, food intake, and fat cell area in SL group were higher than those in NL group while the body temperature was lower until to 13 weeks. By the 13th week, the O₂ consumption, CO₂ output, and heat production of rats in SL group were lower than those in NL group. Meanwhile, the expressions of mitochondrial function related genes such as uncoupling protein 1(UCP1), carnitine palmitoyltransferase 1(CPT1), SIRT1, and mitochondrial biosynthesis regulatory gene peroxisome proliferator-activated receptor coativator-1 (PGC1α) in adipose tissue by the 3rd and 13th week were significantly reduced(P<0.05). After weaning, ω3-PUFA diet significantly reduced weight gain in SL rats, increased UCP1 protein expression, restored energy metabolism level and mitochondrial function related gene expression. In vitro intervention of EPA increased the mitochondrial copy number, the mRNA and protein expression levels of mitochondrial biosynthesis and functional genes, as well as the mitochondrial basic oxygen consumption rate(P<0.05). Conclusion ω3-PUFA improves postnatal overfeeding-induced impairment of the mitochondrial function and biosynthesis of subcutaneous white adipose tissue in rats, which may be an important mechanism for fish oil diet to inhibit the early over-nutrition program and restore the thermogenic metabolism.

Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.

Objective Exploring the effect of Tong luo tang tai(TLTT)on diabetic peripheral neuropathy(DPN)in GK rats with Wnt/β-The influence of the catenin signaling pathway.Methods Fifty GK rats were randomly divided into model group,TLTT high,medium,and low dose groups,and Western medicine group,with 10 rats in each group.Another 10 wistar rats were selected as the normal group.Except for the normal group,all other groups were fed with high fat to prepare DPN rat models.After 15 weeks,the DPN model was successfully prepared,and the rats in each group were treated by gavage.The high,medium,and low dose groups of TLTT were given traditional Chinese medicine TLTT 28 g·kg-1,14 g·kg-1,and 7 g·kg-1,respectively.The western medicine group was given metformin 100 mg·kg-1 and mecobalamin 0.2 mg·kg-1 by gavage.Rats in each group were administered once a day for 8 consecutive weeks.The general state,fasting blood sugar(FBS),thermal contraction latency(TWL),motor nerve conduction velocity(MNCV),and pathological changes in the sciatic nerve tissue were observed under transmission electron microscopy(Real time PCR)Western blot detection of wingless MMTV integration site family member 3A(Wnt3a)β Catenin(β-Catenin,Glycogen Synthesis Kinase-3β Glycogen synthesis kinase-3β,GSK-3β)MRNA and protein expression levels of antagonists(WNT inhibitor factor-1,Wif-1)on the Wnt signaling pathway.Results Compared with the normal group,the model group showed poorer general condition and significant pathological ultrastructural changes in the sciatic nerve.Its FBS level increased(P<0.01),TWL level decreased(P<0.01),and MNCV significantly slowed down(P<0.01).The model group had Wnt3a β-Catenin,GSK-3β MRNA and protein expression levels decreased(P<0.05),while Wif-1 mRNA and protein expression levels increased(P<0.01).After drug intervention,compared with the model group,the general condition and pathological ultrastructure of the sciatic nerve were improved in the TLTT high,medium,low,dose,and Western medicine groups,with a decrease in FBS levels(P<0.01)and an increase in TWL levels(P<0.05).The MNCV of each TLTT dose group and Western medicine group was significantly improved(P<0.01).The Wnt3amRNA of the TLTT high-dose group and Western medicine group was significantly increased(P<0.05),while the Wif-1mRNA of the TLTT high-dose group and Western medicine group was significantly reduced(P<0.05),There was a significant increase in Wnt3 protein in the high-dose and Western medicine groups of TLTT(P<0.01),as well as in the high-dose,medium,and low-dose TLTT and western medicine groups β-Catenin protein significantly increased(P<0.01,P<0.05),with high,medium,and low doses of TLTT and Western medicine group GSK-3β The protein significantly increased(P<0.01,P<0.05),while the Wif-1 protein significantly decreased(P<0.01,P<0.05)in the high and medium dose TTLTT and western medicine groups.Conclusion Tongluo Tangtai can alleviate sciatic nerve injury in DPN to a certain extent,and its mechanism may be related to the activation of Wnt/β,the catenin signaling pathway is involved.

Diabetic peripheral neuropathy （DPN） is characterized by insidious onset， easy misdiagnosis， and progression to severe consequences such as diabetic foot ulcers， gangrene， and amputation. The main pathological features of DPN are nerve cell injuries， such as axonal degeneration and necrosis， segmental demyelination of nerve fibers， and apoptosis of Schwann cells. The phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical pathway that communicates intracellular and extracellular information and regulates biological activities such as cell proliferation， differentiation， apoptosis， autophagy， and migration. It widely affects various cells related to DPN. In recent years， numerous studies have found that the sustained high glucose environment causes abnormalities in the PI3K/Akt signaling pathway. This， in turn， accelerates the occurrence and development of DPN by participating in the pathogenesis of DPN， such as glucose and lipid metabolism， oxidative stress， inflammation， autophagy， apoptosis， and angiogenesis. Therefore， regulating the PI3K/Akt signaling pathway is crucial for the treatment of DPN. Currently， there is a lack of effective measures to slow down or reverse DPN in clinical practice. Traditional Chinese medicine （TCM） has unique advantages in preventing and treating DPN with multiple targets， effects， and components. A large number of animal and clinical studies of TCM treatment of DPN have shown that the PI3K/Akt signaling pathway is an important target for TCM treatment of DPN. Regulating the PI3K/Akt signaling pathway can promote myelin sheath repair and regeneration， delay the process of nerve cell death， and play a role in preventing and treating DPN. However， there is currently no systematic review and summary of this field in China and abroad. Therefore， this article summarized the regulation of the PI3K/Akt signaling pathway and its role in the pathogenesis of DPN， as well as the intervention of effective components of single Chinese medicine or compounds on the PI3K/Akt signaling pathway. This study is expected to provide a reference for the clinical diagnosis and treatment of DPN with TCM， basic research， and drug development.