21:I[432972,["/_next/static/chunks/bb923814e1f4d2e9.js","/_next/static/chunks/dd3ee9f5b7716ca6.js","/_next/static/chunks/4204a0ae82542ca8.js","/_next/static/chunks/1270dead247da766.js","/_next/static/chunks/6e1aa89a642f40be.js","/_next/static/chunks/2d7aa753e81324a8.js","/_next/static/chunks/8ffd0b71567920d8.js","/_next/static/chunks/67ea6dfd21f16c5f.js","/_next/static/chunks/24eb4379f68013fd.js","/_next/static/chunks/b8cd775ffdf935bd.js","/_next/static/chunks/983103cd9eb7b428.js","/_next/static/chunks/263f2cdcb9aa2341.js","/_next/static/chunks/294b9525248c8e5f.js"],"default"] 22:T54f,A classic metabolic concept posits that insulin promotes energy storage and adipose expansion, while catecholamines stimulate release of adipose energy stores by hydrolysis of triglycerides through β-adrenergic receptor (βARs) and protein kinase A (PKA) signaling. Here, we have shown that a key hub in the insulin signaling pathway, activation of p70 ribosomal S6 kinase (S6K1) through mTORC1, is also triggered by PKA activation in both mouse and human adipocytes. Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known βAR-dependent increase of uncoupling protein UCP1 expression and expansion of beige/brite adipocytes (so-called browning) in white adipose tissue (WAT). Mechanistically, PKA directly phosphorylated mTOR and RAPTOR on unique serine residues, an effect that was independent of insulin/AKT signaling. Abrogation of the PKA site within RAPTOR disrupted βAR/mTORC1 activation of S6K1 without affecting mTORC1 activation by insulin. Conversely, a phosphomimetic RAPTOR augmented S6K1 activity. Together, these studies reveal a signaling pathway from βARs and PKA through mTORC1 that is required for adipose browning by catecholamines and provides potential therapeutic strategies to enhance energy expenditure and combat metabolic disease.23:T4b4,In addition to controlling blood pressure, cardiac natriuretic peptides (NPs) can stimulate lipolysis in adipocytes and promote the "browning" of white adipose tissue. NPs may also increase the oxidative capacity of skeletal muscle. To unravel the contribution of NP-stimulated metabolism in adipose tissue compared to that in muscle in vivo, we generated mice with tissue-specific deletion of the NP clearance receptor, NPRC, in adipose tissue (Nprc^AKO ) or in skeletal muscle (Nprc^MKO ). We showed that, similar to Nprc null mice, Nprc^AKO mice, but not Nprc^MKO mice, were resistant to obesity induced by a high-fat diet. Nprc^AKO mice exhibited increased energy expenditure, improved insulin sensitivity, and increased glucose uptake into brown fat. These mice were also protected from diet-induced hepatic steatosis and visceral fat inflammation. These findings support the conclusion that NPRC in adipose tissue is a critical regulator of energy metabolism and suggest that inhibiting this receptor may be an important avenue to explore for combating metabolic disease.24:T551,4-Hydroxyalkenal species are a class of peroxidative products of polyunsaturated fatty acids, which serve as "toxic second messengers" in cellular systems. Investigation of their cellular role is hindered due to the lack of sensitive, reliable, robust method for identification and quantification of these metastable metabolites. Herein, we explored the facile Michael adduct of carnosine with 4-hydroxyalkenal species and developed a sensitive, facile, shotgun lipidomics-based method for quantification of these compounds directly from organic solvent lipid extracts of biological samples. In the study, we extensively examined the factors that may affect the accurate quantification of 4-hydroxyalkenal species and found that this method possessed high reproducibility (<8%) and nearly 3 orders of linear dynamic range with a limit of quantification at lower than 0.56 fmol/μL. Mass levels of 4-hydroxyalkenal species in

#	Concept	H-Index	Publications	Citations
1	Health Sciences	2	2	256
2	Medicine	2	2	256
3	Biochemistry	2	2	256
4	Metabolism	2	2	256
5	Pharmacology	2	2	256

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