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Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect [...]

Proposals for sustainable use of meat industry waste and by-products have seen a remarkable growth in recent decade. This paper aims to shed light on the often-overlooked realm of meat by-products, positioning them as an invaluable source of bioactive peptides and functional ingredients. It emphasized on the first part the main strategies for valorization of meat industry by-products into diverse bioactive peptides, and then it introduces in the second part the diverse and current methods of identification and characterization of bioactive peptides and protein hydrolysates. While the promise of these macromolecules is immense, the paper focuses and takes an in-depth look in the third part at the regulatory and safety barriers hindering their efficient valorization. By addressing regulatory and safety concerns, this review aims to pave the way for a more sustainable and responsible utilization of meat by-products, ensuring not only the economic viability of the meat sector, but also fostering a holistic and safe approach towards enhanced food and animal production sustainability.

The indiscriminate and excessive use of antibiotics has ultimately led to the emergence of bacterial resistant mutants or superbugs. These superbugs are difficult to control with conventional antibiotics. Disabling quorum sensing (QS), a population-density-dependent cell-to-cell communication process used by bacteria to coordinate the expression of virulence genes and biofilm formation, with dietary phytochemicals is emerging as a non-antibiotic strategy to inhibit bacterial pathogenicity. Although curcumin is an anti-QS agent and its delivery to cells has been a challenge due to poor bioavailability, ZnO/curcumin nanocomposites (ZnC-NCs) were fabricated with enhanced delivery of curcumin inside the bacterial superbug Pseudomonas aeruginosaPAO1 for effective inhibition of its QS and biofilm formation. Sustained release of curcumin from ZnC-NCs was observed where 51% curcumin at pH 7.2 and 83% curcumin at pH 5.5 were released within 48 h. ZnC-NCs also decreased the production of virulence factors and biofilm formation without affecting planktonic cell growth. Both LasR and RhlR QS systems were inhibited by ZnC-NCs. ZnC-NCs were also capable of protecting both mice as well as lung epithelial cells from killing by PAO1. The superoxide anions (O2·–) were also found as key players in suppressing PAO1 QS systems by ZnC-NCs. Overall, ZnC-NCs enhanced curcumin bioavailability for effective inhibition of QS signaling in P. aeruginosavia LasR-RhlR suppression and O2·–generation.

Background: Polyunsaturated fatty acid (PUFA) intake is low throughout Latin America. Improving PUFA status could be an effective intervention against chronic disease, but information on sociodemographic and dietary patterning of PUFA status in the region is limited.Objective: To characterize sociodemographic, anthropometric, and dietary predictors of PUFA status biomarkers in adipose tissue among children and their parents from Mesoamerica.Methods: This was a cross-sectional study of 220 children aged 7 to 12 years and 471 parents from capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, and Belize, as well as Tuxtla Gutiérrez in Mexico. The PUFA from gluteal adipose tissue was quantified using gas chromatography. Participants reported sociodemographic information and the type of vegetable oil used for cooking. We estimated percent mean differences in linoleic acid (LA), total long-chain n-6 PUFA (n-6 LCPUFA), α-linolenic acid (ALA), and total long-chain n-3 PUFA (n-3 LCPUFA) between levels of predictors using multivariable-adjusted linear regression models.Results: Country was the strongest predictor of any PUFA, whereas body mass index was positively associated with n-6 LCPUFA in children and adults. Cooking primarily with soybean oil was positively associated with LA in children and adults and ALA in adults. Cooking with canola oil was positively related to n-6 LCPUFA in adults and n-3 LCPUFA in children and adults. Cooking with palm oil was associated with low adipose tissue levels of all n-6 and n-3 PUFA.Conclusions: Adipose tissue PUFA status in Mesoamerica is associated with country of origin and the type of oil used for cooking.

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Bone marrow adipose tissue (MAT) accounts for up to 70% of bone marrow volume in healthy adults and increases further in clinical conditions of altered skeletal or metabolic function. Perhaps most strikingly, and in stark contrast to white adipose tissue, MAT has been found to increase during caloric restriction (CR) in humans and many other species. Hypoleptinemia may drive MAT expansion during CR but this has not been demonstrated conclusively. Indeed, MAT formation and function are poorly understood; hence, the physiological and pathological roles of MAT remain elusive. We recently revealed that MAT contributes to hyperadiponectinemia and systemic adaptations to CR. To further these observations, we have now performed CR studies in rabbits to determine whether CR affects adiponectin production by MAT. Moderate or extensive CR decreased bone mass, white adipose tissue mass, and circulating leptin but, surprisingly, did not cause hyperadiponectinemia or MAT expansion. Although this unexpected finding limited our subsequent MAT characterization, it demonstrates that during CR, bone loss can occur independently of MAT expansion; increased MAT may be required for hyperadiponectinemia; and hypoleptinemia is not sufficient for MAT expansion. We further investigated this relationship in mice. In females, CR increased MAT without decreasing circulating leptin, suggesting that hypoleptinemia is also not necessary for MAT expansion. Finally, circulating glucocorticoids increased during CR in mice but not rabbits, suggesting that glucocorticoids might drive MAT expansion during CR. These observations provide insights into the causes and consequences of CR-associated MAT expansion, knowledge with potential relevance to health and disease.

AGPAT isoforms catalyze the acylation of lysophosphatidic acid (LPA) to form phosphatidic acid (PA). AGPAT2 mutations are associated with defective adipogenesis. Muscle and adipose tissue share common precursor cells. We investigated the role of AGPAT isoforms in skeletal muscle development. We demonstrate that small interference RNA-mediated knockdown of AGPAT1 expression prevents the induction of myogenin, a key transcriptional activator of the myogenic program, and inhibits the expression of myosin heavy chain. This effect is rescued by transfection with AGPAT1 but not AGPAT2. Knockdown of AGPAT2 has no effect. The regulation of myogenesis by AGPAT1 is associated with alterations on actin cytoskeleton. The role of AGPAT1 on actin cytoskeleton is further supported by colocalization of AGPAT1 to areas of active actin polymerization. AGPAT1 overexpression was not associated with an increase in PA levels. Our observations strongly implicate AGPAT1 in the development of skeletal muscle, specifically to terminal differentiation. These findings are linked to the regulation of actin cytoskeleton.

In this study, we report novel and simple chemical syntheses of acyl dihydroxyacetone phosphate (DHAP) and 1-acyl glycero-3-phosphate [lysophosphatidic acid (LPA)], key intermediaries in the formation of glycerolipids containing ester and ether bonds. The synthesis of acyl DHAPs involved acylating the dimethyl ketal of DHAP by acid anhydride using 4-pyrrolidinopyridine as the catalyst, and the resulting product was deketalized by HClO4 in acetone to produce acyl DHAP. The acid anhydride was either added directly or generated in the reaction mixture from the corresponding fatty acid using dicyclohexylcarbodiimide as the condensing agent. Using these methods, a number of acyl DHAPs having short-, medium-, and long-chain saturated and unsaturated acyl groups were synthesized, with overall yields from 37% to 75%. The activities of these acyl DHAPs as substrates for guinea pig liver peroxisomal acyl DHAP:NADPH reductase and alkyl DHAP synthase were then determined. Next, starting from these acyl DHAPs, a variety of LPAs were synthesized by chemical reduction of the ketone group. Biological activities of these LPAs were determined by measuring their relative abilities to release intracellular Ca2+ via the LPA receptor. A combined chemical-enzymatic method is also described to prepare the natural LPA from the racemic mixture.

Chain elongation of fatty acids is an important cellular process and is believed to occur in the endoplasmic reticulum of all eukaroytic cells. Herein we describe the cloning and characterization of a peroxisomal NADPH-specifictrans-2-enoyl-CoA reductase, the key enzyme for a proposed peroxisomal chain elongation pathway. The reductase was solubilized and partially purified from guinea pig liver peroxisomes by affinity chromatography. On SDS-polyacrylamide gel electrophoresis, a 40-kDa band was identified as the enzyme, and its partial amino acid sequence (27 amino acids) was determined. A full-length cDNA for the reductase was cloned from a guinea pig liver cDNA library. The open reading frame of this nucleotide sequence encodes a 302-amino acid polypeptide with a calculated molecular mass of 32.5 kDa. Full-length mouse and human cDNA clones encoding homologous proteins have also been isolated. All of these translated polypeptides have the type I peroxisomal targeting signal, AKL, at the carboxyl terminus. The identity of the cloned enoyl-CoA reductase cDNAs was confirmed by expressing the guinea pig and human cDNAs in Escherichia coli. The His-tagged recombinant enzymes were found to have very high NADPH-specific 2-enoyl-CoA reductase activity with similar properties and specificity as the liver peroxisomal reductase. Both the natural and the recombinant enzyme catalyze the reduction oftrans-2-enoyl-CoAs of varying chain lengths from 6:1 to 16:1, having maximum activity with 10:1 CoA. Northern blot analysis demonstrated that a single transcript of 1.3 kilobases is present in most mouse tissues, with particularly high concentrations in liver and kidney.

The glycerophosphate backbone for triglyceride synthesis is commonly believed to be created through the conversion of dihydroxyacetone phosphate (DHAP) by glycerophosphate dehydrogenase (GPD) to sn-glycerol 3-phosphate (GP), which is then converted by glycerophosphate acyltransferase (GPAT) to 1-acyl-GP. Consistent with this, GPD and GPAT are highly induced during differentiation of mouse 3T3-L1 preadipocytes. While the acyl dihydroxyacetone phosphate (acyl-DHAP) pathway for glycerolipid synthesis is commonly believed to be involved only in glycerol ether lipid synthesis, we report here that during conversion of 3T3-L1 preadipocytes to adipocytes, the specific activity of peroxisomal DHAP acyltransferase (DHAPAT) is increased by 9-fold in 6 days, while acyl-DHAP:NADPH reductase is induced by 5-fold. A parallel increase in the catalase (the peroxisomal marker enzyme) activity is also seen. In contrast, the specific activity of alkyl-DHAP synthase, the enzyme catalyzing the synthesis of the ether bond, is decreased by 60% during the same period. Unlike microsomal GPAT, the induced DHAPAT is found to have high activity at pH 5.5 and is resistant to inhibition by sulfhydryl agents, heat, and proteolysis. On subcellular fractionation, DHAPAT is found to be associated with microperoxisomes whereas GPAT activity is mainly present in microsomes. Northern blot analyses reveal that induction of DHAPAT can be largely explained through increases in DHAPAT mRNA. A comparison of microsomal and peroxisomal glycerolipid synthetic pathways, usingd-[3-3H, U-14C]glucose as the precursor of the lipid glycerol backbone shows that about 40–50% of triglyceride is synthesized via the acyl-DHAP pathway. These results indicate that the acyl-DHAP pathway is important not only for the synthesis of ether lipids, but also for the synthesis of triacylglycerol and other non-ether glycerolipids.

When 1- O-heptadecyl- rac-glycerol was fed (20 mg/g of food) to 19-day-old rats for 10 days, a high incorporation of the heptadecyl group into the 1- O-alk-1′-enyl group of ethanolamine plasmalogens of all tissues was observed. For example, 62% of the alkenyl groups from liver plasmalogen was of the 17:0 variety. The analogous values for other tissues were 62% in kidney, 57% in lung, 57% in heart, 50% in intestine, 43% in erythrocytes, 25% in testis and 8% in brain. The corresponding figures in the control rats (fed normal rat chow) were only 2–3% of 17:0 for all tissues. Available evidence indicates that dietary 1- O-heptadecyl- sn-glycerol is utilized to form tissue plasmalogens without the cleavage of the ether bond. The relevance of these results to the possible dietary ether lipid therapy of patients suffering from congenital ether lipid deficiency is discussed.