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Neuropeptide ACP facilitates lipid oxidation and utilization during long-term flight in locusts

• Authors : Hou, Li; Guo, Siyuan; Wang, Yuanyuan ...

• Source: eLife ; volume 10 ; ISSN 2050-084X

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Decision letter: Neuropeptide ACP facilitates lipid oxidation and utilization during long-term flight in locusts

• Authors : Padinjat, Raghu; Ramanathan, Aravind;

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Author response: Neuropeptide ACP facilitates lipid oxidation and utilization during long-term flight in locusts

• Authors : Hou, Li; Guo, Siyuan; Wang, Yuanyuan

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Figure 3—figure supplement 2. Proposed mechanism of covalent modification of phosphatidylethanolamine (PE) by ophiobolin A (OPA) through a Paal-Knorr-like reaction pathway (Bernoud-Hubac et al., 2004; Amarnath et al., 1991, 1995). ; Addition of the amino group of PE onto the aldehyde moiety of OPA leads to formation of a hemiaminal. Based on the mechanism of the Paal-Knorr reaction and the specific reactivity of OPA, the reaction between PE and OPA is believed to proceed through two potential mechanisms: (i) elimination of a water molecule leading to formation of an imine and subsequent rearrangement to an enamine. Cyclization of the enamine followed by dehydration yields the final pyrrole-containing adduct. (ii) Cyclization of the hemiaminal leads to formation of a dihydroxypyrrolidine. A double elimination of water and double bond shift leads to the final pyrrole-containing adduct. In studies involving the formation of pyrrole adducts from the reaction of 4-oxohexanal and a primary amine, the reaction is known to proceed through the mechanism involving cyclization of the hemiaminal (Amarnath et al., 1995). Under certain conditions, pyrrole adducts are known to be oxidized and the two main expected products are the lactam and hydroxylactam derivatives (Sullivan et al., 2010). In addition, OPA contains an unsaturated aldehyde moiety which is known to readily react with thiols in a Michael addition reaction (Grimsrud et al., 2008). 4-Oxo-2-nonenal, a product of cellular lipid oxidation which has similar reactive functionalities as OPA, has been shown to readily react with N-acetylcysteine (Amarnath and Amarnath, 2015). Interestingly, initial Michael adduct formation of OPA with a thiol would not prevent a subsequent Paal-Knorr reaction with PE and furthermore these two sequential reactions could lead to protein-lipid crosslinking, a potential cause of cytotoxicity.

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Figure 6—figure supplement 3. DMOG inhibits lipid oxidation in RPE cells. ; (A) Basal oxygen consumption rates (OCR) of hRPE treated with BSA-Palmitate conjugates or with BSA alone after treatment with 40 μM Etomoxir, an inhibitor of CPT-1, to validate the increased of OCR are due to fatty acid oxidation (FAO). Data are the mean plus s.e.m. (n=8). (B) Seahorse Flux Analysis full OCR trace showing hRPE cells responding to pre-treatment with DMOG (10 μM) for 24 hr in the presence and absence of BSA, palmitate and etomoxir (see also associated Figure 6—source data 1). Data are the mean plus s.d. (n=6)

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Figure 4. Elevated adipose tissue mitochondrial biogenesis and activity in fat-specific Alk7 knock-out mice on a high fat diet. ; (A–F) Mitochondrial biogenesis assessed by measurements of mitochondrial (mito) DNA content (A and B), citrate synthase activity (C and D), and ATP content (E and F) in epididymal adipose tissue of global Alk7−/− (A, C, E) and fat-specific Alk7fx/−::Ap2CRE (B, D, F) knock-out mice after 16 weeks on a high fat diet (HFD). N = 8 mice per group in all cases. (G and H) Relative mRNA expression of markers of mitochondrial biogenesis and function PGC1a, Hadhb, UCP3, and cytochrome C assessed by quantitative PCR (Q-PCR) in epididymal adipose tissue of global Alk7−/− (G) and fat-specific Alk7fx/−::Ap2CRE (H) knock-out mice after 16 weeks on HFD. N = 6 mice per group in all cases. (I and J) Lipid oxidation in epididymal adipose tissue of global Alk7−/− (I) and fat-specific Alk7fx/−::Ap2CRE (J) knock-out mice. N = 3 mice per group in all cases. *p < 0.05; **p < 0.01; NS, non-significant (mutant vs control). All error bars show mean ± SEM.

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Adipocyte ALK7 links nutrient overload to catecholamine resistance in obesity

• Authors : Guo, Tingqing; Marmol, Patricia; Moliner, Annalena ...

• Source: eLife ; volume 3 ; ISSN 2050-084X

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Convergent changes in muscle metabolism depend on duration of high-altitude ancestry across Andean waterfowl

• Authors : Dawson, Neal J; Alza, Luis; Nandal, Gabriele ...

• Source: eLife ; volume 9 ; ISSN 2050-084X

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