Effects of aging-induced obesity on the transcriptional expression of adipogenesis and thermogenic activity in the gonadal white adipose, brown adipose, and skeletal muscle tissues.

PURPOSE: Aging is closely associated with chronic metabolic diseases, such as obesity, which lead to increased adiposity, skeletal muscle wasting, and imbalanced cellular energy metabolism. However, transcriptional profiles representing energy imbalances in aging-induced obesity are not fully understood. Thus, this study aimed to investigate the candidate genes predominantly regulated in aging-related obesity in spontaneously aged mice. METHODS: Male C57BL/6J mice were divided into three age groups according to age: 2- (young), 12- (middle-aged), and 24- (old) months. Body weight and body composition parameters were measured in all mice. Gonadal white adipose tissue (gWAT), brown adipose tissue (BAT), and skeletal muscle (SM) were dissected and weighed. The target tissues were assessed using biochemical and histological assays. RESULTS: Aging-induced obesity increased adipose mass and decreased SM weight through processes of adipocyte hypertrophy; however, recruitment of modulating adipogenesis-inducing transcription factors did not occur. Among adipokines, leptin level was greatly increased in the gWAT during aging. Interestingly, the ß2-adrenergic receptor had a higher affinity than the ß3-adrenergic receptor in aging-induced obesity. For the thermogenic regulation through ß-adrenergic receptors (ß-ARs), a declined uncoupling protein-1 (UCP-1) in the BAT was relevant to aging-induced obesity. CONCLUSION: Aging-induced obesity increases leptin levels in adipocytes and decreases UCP-1 in BAT through ß-ARs, according to transcriptional gene profiling. WAT browning increases energy expenditure due to exercise training adaptations. Further research is needed to discover more effective methods, such as exercise, against aging-induced obesity.

Hormesis effects of sulfoxaflor on Aphis gossypii feeding, growth, reproduction behaviour and the related mechanisms.

Sulfoxaflor, an important alternative insecticide in integrated pest management (IPM) strategies, can effectively control sap-feeding insect pests such as Aphis gossypii. Although the side effects of sulfoxaflor have recently attracted widespread attention, its toxicological characteristics and mechanisms are still largely undefined. Therefore, the biological characteristics, life table and feeding behaviour of A. gossypii were studied to evaluate the hormesis effect of sulfoxaflor. Then, the potential mechanisms of induced fecundity associated with the vitellogenin (Ag. Vg) and vitellogenin receptor (Ag. VgR) genes were investigated. Although the LC10 and LC30 concentrations of sulfoxaflor significantly reduced the fecundity and net reproduction rate (R0) of the directly exposed sulfoxaflor-resistant and susceptible aphids, hormesis effects on fecundity and R0 were observed in the F1 generation of Sus A. gossypii when the parental generation was exposed to the LC10 of sulfoxaflor. Moreover, the hormesis effects of sulfoxaflor on phloem feeding were observed in both A. gossypii strains. Additionally, enhanced expression levels and protein content of Ag. Vg and Ag. VgR were observed in progeny generations when F0 was subjected to the trans- and multigenerational sublethal sulfoxaflor exposure. Therefore, sulfoxaflor-induced resurgence might occur in A. gossypii after exposure to sublethal concentrations. Our study could contribute to a comprehensive risk assessment and provide convincing reference to optimize sulfoxaflor in IPM strategies.

Sulfoxaflor adversely influences the biological characteristics of Coccinella septempunctata by suppressing vitellogenin expression and predation activity.

Sulfoxaflor is a widely used sulfoximine insecticide that has been regarded as an important alternative insecticide for IPM strategies, but a comprehensive study of its potential ecological toxicity is still lacking. In the present work, the growth, longevity, predation and reproduction toxicity of Coccinella septempunctata caused by sulfoxaflor were evaluated. In addition, the potential mechanisms of decreased fecundity in C. septempunctata were investigated by analyzing the transcriptional and protein levels of reproduction-related gene vitellogenin (Vg). In a 20-day acute contact toxicity test, decreased survival proportion, pupation rate, adult emergence ratio, and increased hazard quotient (HQ) values were observed. Moreover, sublethal dosages of sulfoxaflor significantly inhibited the predation, longevity, fecundity and net reproduction rate of progeny. In addition, LR30 of sulfoxaflor dramatically down-regulate the mRNA-expression (F0: 65.38-fold, F1: 2.24-fold) and protein content (F0: 1.35-fold, F1: 1.36-fold) of Vg in the F0 and F1 generations. These results suggested that sulfoxaflor could inhibit the gene and protein content of Vg, thereby reducing the fecundity of C. septempunctata. Our study indicated that sulfoxaflor has potential risks to parent and progeny generations of C. septempunctata. These results provide valuable reference for optimal usage of sulfoxaflor in IPM systems.

Comparative Toxicity and Joint Effects of Chlorantraniliprole and Carbaryl Against the Invasive Spodioptera frugiperda (Lepidoptera: Noctuidae).

Fall armyworm, Spodoptera frugiperda, is one of the most devastating invasive pests in China. Chlorantraniliprole (CH) is currently the main agent for controlling S. frugiperda. Carbaryl (CA) has been widely used as a foliar treatment to control S. frugiperda, although the pest has become highly resistant to it. This study investigates the comparative toxicity and joint effects of CH and CA on S. frugiperda. Time-toxicity results showed that CH had high toxicity to 1st and 3rd instar larvae, whereas CA had very low toxicity to 1st and 3rd instar larvae. The mixtures of CH and CA at different mass ratios showed strong synergistic effects on toxicity, and the mass ratio of 2:1 exhibited the highest toxicity to S. frugiperda. Furthermore, the synergistic toxicity of CH and CA at the 2:1 mass ratio (CH+CA) was also verified in field populations of S. frugiperda. The life-history parameters showed that CH+CA dramatically decreased the survival rate and fecundity of the parent population (F0) compared with CH treatment at the same concentration. Besides, CH and CH+CA mixture showed induction effect on cytochrome P450s and glutathione-S-transferases (GSTs) activities in S. frugiperda, with cytochrome P450s enzyme responding the fastest. In conclusion, this research found CH+CA provided synergistic effects on the toxicity and the sublethal effect on larvae. The joint effects on the life-history parameters and the detoxifying enzymes in S. frugiperda, may be useful for implementing IPM programs against this Lepidoptera pest.

Field-evolved resistance to 11 insecticides and the mechanisms involved in Helicoverpa armigera (Lepidoptera: Noctuidae).

BACKGROUND: To understand the ongoing resistance of cotton bollworm, Helicoverpa armigera, the sensitivity of five field populations to commonly used insecticides, indoxacarb, abamectin, methoxyfenozide, chlorfenapyr, chlorantraniliprole, spinetoram, lambda-cyhalothrin, carbosulfan, metaflumizone, chlorpyrifos, and flufenoxuron, were evaluated. Furthermore, the biochemical and molecular mechanisms of field-evolved resistance in H. armigera were also investigated. RESULTS: Five field populations of H. armigera showed moderate resistance to indoxacarb, chlorantraniliprole, metaflumizone, methoxyfenozide, carbosulfan and lambda-cyhalothrin. The resistance ratio (RR) of indoxacarb was significantly correlated with glutathione-S-transferases (GSTs) activity (r = 0.913, P = 0.011). Methoxyfenozide RR was largely correlated with cytochrome P450s activity (r = 0.860, P = 0.028). Besides, six cytochrome P450s genes of CYP4L5 in AQP, CYP6B7 and CYP9A14 in HDP and BDP, CYP9A17V2 in HDP and YSP, CYP332A1 in HDP, LFP, AQP and YSP, CYP337B1 in YSP, and two GSTs genes of GSTd1 and GSTs1 in HDP were overexpressed (>5-fold). Moreover, indoxacarb RR was positively correlated with the overexpression of GSTs1, GSTd1 and CYP9A14 genes (r = 0.880, 0.98 and 0.86, P = 0.021, 0.001 and 0.028, respectively). The transcript of CYP9A17V2 and CYP337B1 were found to be correlated with metaflumizone RR (r = 0.950, P = 0.004) and carbosulfan RR (r = 0.850, P = 0.033), respectively. CONCLUSION: H. armigera can be effectively controlled using abamectin, chlorfenapyr, chlorpyrifos and spinetoram in Hebei and Shandong provinces. The present study demonstrated that the relative expression level of GSTs1, GSTd1, CYP9A14, CYP9A17V2 and CYP337B1 genes were significantly correlated with the resistance ratio to indoxacarb, metaflumizone and carbosulfan in field H. armigera.

Overexpression of Multiple UDP-Glycosyltransferase Genes Involved in Sulfoxaflor Resistance in Aphis gossypii Glover.

UDP-glycosyltransferases (UGTs) are major phase II enzymes involved in the metabolic detoxification of xenobiotics. In this study, two UGT-inhibitors, 5-nitrouracil and sulfinpyrazone, significantly increased sulfoxaflor toxicity against sulfoxaflor-resistant (Sul-R) Aphis gossypii, whereas there were no synergistic effects in susceptible (Sus) A. gossypii. The activity of UGTs in the Sul-R strain was significantly higher (1.35-fold) than that in the Sus strain. Further, gene expression determination demonstrated that 11 of 23 UGT genes were significantly upregulated (1.40- to 5.46-fold) in the Sul-R strain, among which the expression levels of UGT350A2, UGT351A4, UGT350B2, UGT342C2, and UGT343C2 could be induced by sulfoxaflor. Additionally, knockdown of UGT350A2, UGT351A4, UGT350B2, and UGT343C2 using RNA interference (RNAi) significantly increased sensitivity (1.57- to 1.76-fold) to sulfoxaflor in the Sul-R strain. These results suggested that UGTs might be involved in sulfoxaflor resistance in A. gossypii. These findings will facilitate further work to validate the functional roles of these UGT genes in sulfoxaflor resistance.

Overexpression of ATP-binding cassette transporters associated with sulfoxaflor resistance in Aphis gossypii glover.

BACKGROUND: Sulfoxaflor is a new insecticide for controlling against Aphis gossypii in the field. ATP-binding cassette (ABC) transporters belong to a large superfamily of proteins and play an important role in the detoxification process. However, the potential role of ABC transporters in sulfoxaflor resistance in A. gossypii is unknown. RESULTS: In this study, an ABC transporter inhibitor, verapamil, dramatically increased the toxicity of sulfoxaflor in the resistant population with a synergistic ratio of 8.55. However, verapamil did not synergize sulfoxaflor toxicity in the susceptible population. The contents of ABC transporters were significantly increased in the Sul-R population. Based on RT-qPCR analysis, 10 of 23 ABC transcripts, ABCA1, ABCA2, ABCB1, ABCB5, ABCD1, ABCG7, ABCG16, ABCG26, ABCG27, and MRP7, were up-regulated in the Sul-R population compared to the Sus population. Meanwhile, inductive effects of ABCA1, ABCD1, ABCG7 and ABCG26 by sulfoxaflor were found in A. gossypii. Furthermore, knockdown of ABCA1 and ABCD1 using RNAi significantly increased the sulfoxaflor sensitivity in Sul-R aphids. CONCLUSION: These results suggested that ABC transporters, especially the ABCA1 and ABCD1 genes, might be related with sulfoxaflor resistance in A. gossypii. This study will promote further work to validate the functional roles of these ABCs in sulfoxaflor resistance and might be helpful for the management of sulfoxaflor-resistant A. gossypii.