Cardiotrophin-1 (CT-1) is a member of the gp130 family of cytokines. We observed that ct-1(-/-) mice develop mature-onset obesity, insulin resistance, and hypercholesterolemia despite reduced calorie intake. Decreased energy expenditure preceded and accompanied the development of obesity. Acute treatment with rCT-1 decreased blood glucose in an insulin-independent manner and increased insulin-stimulated AKT phosphorylation in muscle. These changes were associated with stimulation of fatty acid oxidation, an effect that was absent in AMPKα2(-/-) mice. Chronic rCT-1 treatment reduced food intake, enhanced energy expenditure, and induced white adipose tissue remodeling characterized by upregulation of genes implicated in the control of lipolysis, fatty acid oxidation, and mitochondrial biogenesis and genes typifying brown fat phenotype. Moreover, rCT-1 reduced body weight and corrected insulin resistance in ob/ob and in high-fat-fed obese mice. We conclude that CT-1 is a master regulator of fat and glucose metabolism with potential applications for treatment of obesity and insulin resistance.

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A new formulation of dry fermented sausage, including ingredients that contribute to improve the nutritional and health benefits of this type of products is presented. Se yeast (2 g/kg), iodized salt (26 g/kg), linseed:algae (3:2) emulsion (62.5 g/kg), and lyophilized water extract of Melissa officinalis L. as source of natural antioxidants (686 mg/kg), allowed to obtain dry fermented sausages with technological and sensorial properties similar to traditional ones.From the nutritional standpoint, a 50 g portion of this product would cover a 100 % of the recommended intake value for Se, a 70 % of DRI for iodine, and a 40 % and 100 % of the labeling reference intake for α-linolenic and EPA+DHA, respectively. The ω-6/ω-3 ratio decreased from 15.7 in the control product to 1.96 in the modified one.Despite the high PUFA content, no oxidation signs were detected by TBARS (<0.15 mg MDA/kg) and volatile compounds, pointing at the effectiveness of the proposed natural antioxidant from Melissa officinalis.The modified formulation presented good acceptability for panelists and similar appearance, odor, taste and juiciness with control products.

An evaluation of the capacity of a lyophilized water extract of borage leaves to delay the lipid oxidation process in dry fermented sausages enriched with ω-3 PUFAs has been performed. Lyophilized extract (340ppm) showed an antioxidant capacity equivalent to 200ppm of a butylhydroxyanisol (BHA) and butylhydroxytoluene (BHT) mixture. Two batches of dry fermented sausages enriched in ω-3 PUFA were developed. One of them was supplemented with a synthetic antioxidants mixture (200ppm of BHA+BHT) and the other one with natural antioxidants (340ppm of lyophilized water extract of borage leaves). Furthermore, a traditional formulation of this type of dry fermented sausage (Control), was also manufactured. The natural extract gave rise to lower amount of volatile compounds (including hexanal), than the mixture of synthetic antioxidants (2202 and 2713ng dodecane/g dry matter, respectively). TBARS and Cholesterol Oxidation Products (COPs) did not show significant differences between products with different antioxidants. The sensorial analysis showed that lyophilized water extracts of borage leaves did not affect the sensorial properties of the products. From the economical and safety standpoints, the use of a by-product (borage leaves) and water as extracting solvent are valuable alternatives for obtaining natural antioxidants to be added to dry fermented sausages enriched in ω-3 PUFA.

This article is available online at http://www.jlr.org effects by interacting with the glycoprotein 130 (gp130)/ leukemia inhibitory factor receptor heterodimer ( 1 ). Adipose tissue has been identifi ed as a source of CT-1 ( 2 ), and this cytokine is capable of activating major signaling pathways involved in metabolic control in adipocytes ( 3 ). Moreover, it has been reported that CT-1 levels are raised in obesity and metabolic syndrome ( 2 ), suggesting that CT-1 could be a new marker for obesity and related diseases. A recent study by our group has revealed that CT-1 is a key regulator of energy homeostasis, as well as of glucose and lipid metabolism ( 4 ). Thus, chronic recombinant CT-1 (rCT-1) treatment reduced body weight and corrected insulin resistance in ob/ob and high-fat-fed obese mice by reducing food intake and enhancing energy expenditure. Moreover, rCT-1 induced dramatic white adipose tissue remodeling characterized by the upregulation of genes implicated in the control of fatty acid oxidation, mitochondrial biogenesis, and lipolysis. In this context, it has been reported that adipocytes from rCT-1-treated mice exhibited an increased lipolytic response to isoproterenol, while adipocytes from old obese CT-1 -null mice responded poorly to isoproterenol, suggesting that CT-1 might play a role in the regulation of lipolysis ( 4 ). However, the mechanism underlying the lipolytic action of CT-1 still remains unknown.During lipolysis, intracellular triacylglycerol (TAG) is hydrolyzed through the consecutive action of three major lipases: adipose triglyceride lipase (ATGL/desnutrin), Abbreviations: AdPLA , adipocyte phospholipase A2; AICAR, aminoimidazole carboxamide ribonucleotide; ATGL, adipose triglyceride lipase (desnutrin); CGI-58, comparative gene identifi cation-58; cGMP, cyclic guanosine monophosphate; CT-1, cardiotrophin-1; DAG, diacylglycerol; Gi, inhibitory guanine nucleotide binding protein; gp130, glycoprotein 130; Gs, stimulatory guanine nucleotide binding protein; G0S2, G0/G1 switch gene 2; HPTLC, high-performance TLC; HSL, hormone sensitive lipase; IL, interleukin; MAG, monoacylglycerol; PDE3B, phosphodiesterase 3B; PK, protein kinase; rCT-1, recombinant cardiotrophin-1; TAG, triacylglycerol. 1 M. Bustos and M. J. Moreno-Aliaga contributed equally to the work.