Dysregulation of epicardial adipose tissue in cachexia due to heart failure. the role of natriuretic peptides and cardiolipin

Background: Cachexia worsens long-term prognosis of patients with heart failure (HF). Effective treatment of cachexia is missing. We seek to characterize mechanisms of cachexia in adipose tissue, which could serve as novel targets for the treatment. Methods: The study was conducted in advanced HF patients (n = 52; 83% male patients) undergoing heart transplantation. Patients with ≥7.5% non-intentional body weight (BW) loss during the last 6 months were rated cachectic. Clinical characteristics and circulating markers were compared between cachectic (n = 17) and the remaining, BW-stable patients. In epicardial adipose tissue (EAT), expression of selected genes was evaluated, and a combined metabolomic/lipidomic analysis was performed to assess (i) the role of adipose tissue metabolism in the development of cachexia and (ii) potential impact of cachexia-associated changes on EAT-myocardium environment. Results: Cachectic vs. BW-stable patients had higher plasma levels of natriuretic peptide B (BNP; 2007 ± 1229 vs. 1411 ± 1272 pg/mL; P = 0.010) and lower EAT thickness (2.1 ± 0.8 vs. 2.9 ± 1.4 mm; P = 0.010), and they were treated with ~2.5-fold lower dose of both β-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACE/ARB-inhibitors). The overall pattern of EAT gene expression suggested simultaneous activation of lipolysis and lipogenesis in cachexia. Lower ratio between expression levels of natriuretic peptide receptors C and A was observed in cachectic vs. BW-stable patients (0.47 vs. 1.30), supporting activation of EAT lipolysis by natriuretic peptides. Fundamental differences in metabolome/lipidome between BW-stable and cachectic patients were found. Mitochondrial phospholipid cardiolipin (CL), specifically the least abundant CL 70:6 species (containing C16:1, C18:1, and C18:2 acyls), was the most discriminating analyte (partial least squares discriminant analysis; variable importance in projection score = 4). Its EAT levels were higher in cachectic as compared with BW-stable patients and correlated with the degree of BW loss during the last 6 months (r = −0.94; P = 0.036). Conclusions: Our results suggest that (i) BNP signalling contributes to changes in EAT metabolism in cardiac cachexia and (ii) maintenance of stable BW and ‘healthy’ EAT-myocardium microenvironment depends on the ability to tolerate higher doses of both ACE/ARB inhibitors and β-adrenergic blockers. In line with preclinical studies, we show for the first time in humans the association of cachexia with increased adipose tissue levels of CL. Specifically, CL 70:6 could precipitate wasting of adipose tissue, and thus, it could represent a therapeutic target to ameliorate cachexia

Определение уровня биоконверсии питательных веществ у приматов

The results of studies on feeding biologically active additives suspensions of chlorella and Bactistatin in the diets of primates are presented. Its positive effect on the bioconversion of diets was experimentally established. The coefficients of digestibility of nutrients with dry chlorella and fishmeal in the composition of complete feed were determined. The obtained experimental data are important for the preparation of scientifically grounded and optimally balanced feeding rations, taking into account the digestibility of feed. This will optimally balance feed rations for all nutrients, while reducing feed costs and, as a result, increasing the profitability of keeping primates. It was found that the introduction of chlorella powder and fishmeal into the diet improves protein absorption by 6.83 and 5.66%, crude fat - by 2.61 and 3.92, crude fiber - by 4.78 and 4.25, NFES - by 4.15 and 2.26, crude ash - by 18.93 and 12.08%. The use of calcium and phosphorus macronutrients was higher in the 3rd experimental group, which received 14% chlorella in the main diet by 1.38 and 8.07%, respectively. In the 5th experimental group, which received 18.26% of the main ration of fishmeal, calcium was absorbed more efficiently by 4.77, and phosphorus - by 1.21%. The use of diet supplements in the form of a suspension of chlorella and Bactistatin helped to stimulate the bioconversion of nutrients in the diets used in the nursery for feeding monkeys, and enabled to maintain the main blood parameters within physiological norms.Приведены результаты исследований по скармливанию в рационах приматов биологически активных добавок – суспензии хлореллы и Бактистатина, экспериментально установлено их положительное влияние на биоконверсию рационов. Определены коэффициенты переваримости питательных веществ при использовании сухой хлореллы и рыбной муки в составе полнорационных комбикормов. Полученные экспериментальные данные имеют важное значение для составления научно обоснованных и оптимально сбалансированных рационов кормления с учётом переваримости кормов. Это, в свою очередь, позволит оптимально сбалансировать рационы кормления по всем питательным веществам, обеспечив при этом снижение стоимости кормов и, как следствие, увеличить рентабельность содержания приматов. Установлено, что введение в состав рациона порошка хлореллы и рыбной муки улучшает усвоение протеина на 6,83 и 5,66 %, сырого жира – на 2,61 и 3,92, сырой клетчатки – на 4,78 и 4,25, БЭВ – на 4,15 и 2,26, сырой золы – на 18,93 и 12,08 %. Использование макроэлементов кальция и фосфора было выше в 3-й опытной группе, получавшей в основном рационе 14 % хлореллы, на 1,38, и 8,07 % соответственно. В 5-й опытной группе, которая получала 18,26 % к основному рациону рыбной муки, кальций усваивался эффективнее на 4,77, а фосфор – на 1,21 %. Применение БАД в виде суспензии хлореллы и Бактистатина способствовало стимулированию биоконверсиии питательных веществ рационов, применяемых в питомнике для кормления обезьян, и позволяло сохранять основные показатели крови в пределах физиологических норм

Long-term space flight simulation reveals infradian rhythmicity in human Na(+) balance

The steady-state concept of Na(+) homeostasis, based on short-term investigations of responses to high salt intake, maintains that dietary Na(+) is rapidly eliminated into urine, thereby achieving constant total-body Na(+) and water content. We introduced the reverse experimental approach by fixing salt intake of men participating in space flight simulations at 12 g, 9 g, and 6 g/day for months and tested for the predicted constancy in urinary excretion and total-body Na(+) content. At constant salt intake, daily Na(+) excretion exhibited aldosterone-dependent, weekly (circaseptan) rhythms, resulting in periodic Na(+) storage. Changes in total-body Na(+) (±200-400 mmol) exhibited longer infradian rhythm periods (about monthly and longer period lengths) without parallel changes in body weight and extracellular water and were directly related to urinary aldosterone excretion and inversely to urinary cortisol, suggesting rhythmic hormonal control. Our findings define rhythmic Na(+) excretory and retention patterns independent of blood pressure or body water, which occur independent of salt intake