Transcriptional determinants of lipid mobilization in human adipocytes.

Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins. On the basis of its strong relationship with multiple readouts of lipolysis in patient samples, we performed mechanistic studies on one hit, ZNF189, which encodes the zinc finger protein 189. Using mass spectrometry and chromatin profiling techniques, we show that ZNF189 interacts with the tripartite motif family member TRIM28 and represses the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). The regulation of lipid mobilization by ZNF189 requires PDE1B2, and the overexpression of PDE1B2 is sufficient to attenuate hormone-stimulated lipolysis. Thus, our work identifies the ZNF189-PDE1B2 axis as a determinant of human adipocyte lipolysis and highlights a link between chromatin architecture and lipid mobilization.

Impaired phosphocreatine metabolism in white adipocytes promotes inflammation.

The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.

An index to measure the activity attitude of broilers in extensive system.

In organic poultry production it is important to rear animals with a dynamic attitude to take advantage of outdoor areas. Farmers are reluctant to use such strains due to their lower productivity and older slaughtering age. However, fast growing lines grown in organic system often suffer poor health and welfare conditions. The kinetic metabolism of chickens is correlated with different types of muscle fiber: type I (in red muscles or oxidative) for prolonged and moderate movement and type II (in white muscles or glycogenic) for fast movements. Red muscle metabolism produces energy mainly by ß-oxidation of Highly Unsaturated n-3 Fatty Acids (HUFA). Accordingly, kinetic activity causes higher consume of HUFA in red muscles than in white muscles, so the ratio between n-3 HUFA and their precursor C18:3 n-3 (ALA) is likely to be smaller in red than in white muscles. However, these ratios are highly affected by the environment. To reduce the effect of environmental variables, we propose an "Activity index" as the difference between n-3 HUFA/ALA in white and red muscle within the same bird. This index, measured after slaughtering, should represent the activity performed by the chicken during its life. Given that birds in good health had the possibility of moving, the "Activity index" would measure the activity actually performed by the animals. Should birds of a given strain show a higher activity level, this would be an indication of the suitability of that strain to outdoor systems. This work verified the application of this "Activity index" on 90 birds from 6 genetic strains with known kinetic behavior reared in an experimental farm. The "Activity index" was also tested on chicken strains collected form commercial organic farms. The results confirmed that strains recognized for higher kinetic attitude actually walked more and their behavior was clearly detected by the "Activity index" estimated from their muscles.

The bright and the dark sides of L-carnitine supplementation: a systematic review.

BACKGROUND: L-carnitine (LC) is used as a supplement by recreationally-active, competitive and highly trained athletes. This systematic review aims to evaluate the effect of prolonged LC supplementation on metabolism and metabolic modifications. METHODS: A literature search was conducted in the MEDLINE (via PubMed) and Web of Science databases from the inception up February 2020. Eligibility criteria included studies on healthy human subjects, treated for at least 12 weeks with LC administered orally, with no drugs or any other multi-ingredient supplements co-ingestion. RESULTS: The initial search retrieved 1024 articles, and a total of 11 studies were finally included after applying inclusion and exclusion criteria. All the selected studies were conducted with healthy human subjects, with supplemented dose ranging from 1 g to 4 g per day for either 12 or 24 weeks. LC supplementation, in combination with carbohydrates (CHO) effectively elevated total carnitine content in skeletal muscle. Twenty-four-weeks of LC supplementation did not affect muscle strength in healthy aged women, but significantly increased muscle mass, improved physical effort tolerance and cognitive function in centenarians. LC supplementation was also noted to induce an increase of fasting plasma trimethylamine-N-oxide (TMAO) levels, which was not associated with modification of determined inflammatory nor oxidative stress markers. CONCLUSION: Prolonged LC supplementation in specific conditions may affect physical performance. On the other hand, LC supplementation elevates fasting plasma TMAO, compound supposed to be pro-atherogenic. Therefore, additional studies focusing on long-term supplementation and its longitudinal effect on the cardiovascular system are needed.

Organic carbon pools and soil biological fertility are affected by land use intensity in Mediterranean ecosystems of Sardinia, Italy.

Soil quality is mainly studied from the chemical and physical point of view, whereas soil biochemical and microbiological parameters are relatively more scarcely explored to assess the effect of management practices. This study aimed to evaluate soil organic carbon (SOC) and its pools; soil microbial activity parameters; and the Biological Fertility Index (BFI), in six land uses characteristics of the Mediterranean basin in north-eastern Sardinia. These land uses differed in management intensity and consisted of: tilled vineyard (TV), no tilled grassed vineyard (GV), former vineyards (FV), hay crop and pasture (HC and PA), cork oak forest (CO). Significant differences among ecosystems were found in most cases in (SOC), the related pools (total extractable carbon, humic and fulvic acids, not humified, not extractable), humification parameters (degree, rate and index of humification), and soil microbial activity (microbial carbon, respiration, metabolic quotient, and mineralization quotient). Pasture and cork oak forest showed in average a better soil quality for most biochemical and microbial parameters in comparison with the other ecosystems. The index of soil biological fertility (BFI) was higher under cork oak forest which is supposed to be the most sustainable ecosystem in the long term in this environment, able to maintain soil biological fertility and microbial diversity.