Proteomic analysis of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention

Objective:To investigate the proteomic characteristics of overweight/obesity and related abnormal glucose and lipid metabolism caused by phlegm-dampness retention to identify related biomarkers.Methods:Seventy-one subjects were enrolled in the study.We assessed blood glucose,blood lipids,body mass index(BMI),and phlegm-dampness pattern,which was confirmed by a traditional Chinese medicine clinician.Of the participants,we included healthy participants with normal weight(NW,n=23),overweight/obese participants with normal metabolism(ONM,n=19),overweight/obese participants with pre-diabetes(OPD,n=12),and overweight/obese participants with marginally-elevated blood lipids(OML,n=17).Among them,the ONM,OPD,and OML groups were diagnosed with phlegmdampness pattern.The data-independent acquisition(DIA)method was first used to analyze the plasma protein expression of each group,and the relevant differential proteins of each group were screened.The co-expressed proteins were evaluated by Venn analysis.The pathway analyses of the differential proteins were analyzed using Ingenuity Pathway Analysis(IPA)software.Parallel reaction monitoring(PRM)was used to verify the differential and common proteins in each group.Results:After comparing ONM,OPD,and OML groups with NW group,we identified the differentially expressed proteins(DEPs).Next,we determined the DEPs among OPD,OML,and ONM groups.Using Venn analysis of the DEPs in each group,24 co-expressed proteins were screened.Two co-expressed proteins were verified by PRM.IPA analysis showed that pathways including LXR/RXR activation,acute phase response signaling,and FXR/RXR activation were common to all three groups of phlegmdamp overweight/obesity participants.However,the activation or inhibition of these pathways was different among the three groups.Conclusion:Participants with overweight/obesity have similar proteomic characteristics,though each type shows specific proteomic characteristics.Two co-expressed proteins,VTN and ORM1,are potential biomarkers for glucose and lipid metabolism diseases with overweight/obesity caused by phlegmdampness retention.

Interaction between hepatitis C virus and metabolic factors

Hepatitis C virus (HCV) infection disrupts the normal metabolism processes, but is also influenced by several of the host’s metabolic factors. An obvious and significantly detrimental pathophysiological feature of HCV infection is insulin resistance in hepatic and peripheral tissues. Substantial research efforts have been put forth recently to elucidate the molecular mechanism of HCV-induced insulin resistance, and several cytokines, such as tumor necrosis factor-α, have been identified as important contributors to the development of insulin resistance in the distant peripheral tissues of HCV-infected patients and animal models. The demonstrated etiologies of HCV-induced whole-body insulin resistance include oxidative stress, lipid metabolism abnormalities, hepatic steatosis and iron overload. In addition, myriad effects of this condition have been characterized, including glucose intolerance, resistance to antiviral therapy, progression of hepatic fibrosis, development of hepatocellular carcinoma, and general decrease in quality of life. Metabolic-related conditions and disorders, such as visceral obesity and diabetes mellitus, have been shown to synergistically enhance HCV-induced metabolic disturbance, and are associated with worse prognosis. Yet, the molecular interactions between HCV-induced metabolic disturbance and host-associated metabolic factors remain largely unknown. The diet and lifestyle recommendations for chronic hepatitis C are basically the same as those for obesity, diabetes, and metabolic syndrome. Specifically, patients are suggested to restrict their dietary iron intake, abstain from alcohol and tobacco, and increase their intake of green tea and coffee (to attain the beneficial effects of caffeine and polyphenols). While successful clinical management of HCV-infected patients with metabolic disorders has also been achieved with some anti-diabetic (i.e., metformin) and anti-lipid (i.e., statins) medications, it is recommended that sulfonylurea and insulin be avoided.