The autophagy protein ATG9A enables lipid mobilization from lipid droplets

The multispanning membrane protein ATG9A is a scramblase that flips phospholipids between the two membrane leaflets, thus contributing to the expansion of the phagophore membrane in the early stages of autophagy. Herein, we show that depletion of ATG9A does not only inhibit autophagy but also increases the size and/or number of lipid droplets in human cell lines and C. elegans. Moreover, ATG9A depletion blocks transfer of fatty acids from lipid droplets to mitochondria and, consequently, utilization of fatty acids in mitochondrial respiration. ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes.

Ilex paraguariensisA. St.-Hil. (Yerba Mate) Differently Regulates the Lipid Mobilization and, Irisin and Lactate Levels in Sedentary and Chronic Swimming Mice

Healthy mice were submitted or not to daily chronic swimming and/or daily yerba mate (YM) infusion intake and had their bloods analyzed after four weeks. We hypothesized that daily intake of YM may act differently on lipid mobilization and, on the creatine, lactate and irisin levels in sedentary mice and those submitted to chronic exercise. The groups were (n=48): YM-non-treated control (NTC), YM-non-treated swimming control (NSC), non-roasted YM (NRY), roasted YM (RY), swimming plus non-roasted YM (SNRY), swimming plus roasted YM (SRY). No significant (P>0.05) difference was observed concerning creatine phosphoskinase (CPK) value. Lactate level decreased significantly (P<0.05) for SNRY and SRY, suggesting accelerated lipid mobilization and glycogen sparing potential. There was significant (P<0.05) body weight loss in all, except for NTC. Higher weight loss in NRY, RY, SNR and SRY indicated greater lipid mobilization. Thiobarbituric acid reactive substances (TBARS) and irisin had significantly (P<0.05) higher values for RY. This is first report that deals with the effect of YM consumption on serum irisin level. Major amounts of caffeic acid derivatives, slightly increased caffeine and less amount of rutin may be responsible by accelerated lipoperoxidation in sedentary healthy mices chronically treated with roasted YM. Chronically consumed YM plus swimming aid in healthy weight loss. Sedentary lifestyle plus roasted YM chronic consumption may cause accelerated lipid mobilization and increased TBARS production via irisin overexpression leading to an increase in lipoperoxidation.

A bone-specific adipogenesis pathway in fat-free mice defines key origins and adaptations of bone marrow adipocytes with age and disease

Bone marrow adipocytes accumulate with age and in diverse disease states. However, their origins and adaptations in these conditions remain unclear, impairing our understanding of their context-specific endocrine functions and relationship with surrounding tissues. In this study, by analyzing bone and adipose tissues in the lipodystrophic 'fat-free' mouse, we define a novel, secondary adipogenesis pathway that relies on the recruitment of adiponectin-negative stromal progenitors. This pathway is unique to the bone marrow and is activated with age and in states of metabolic stress in the fat-free mouse model, resulting in the expansion of bone marrow adipocytes specialized for lipid storage with compromised lipid mobilization and cytokine expression within regions traditionally devoted to hematopoiesis. This finding further distinguishes bone marrow from peripheral adipocytes and contributes to our understanding of bone marrow adipocyte origins, adaptation, and relationships with surrounding tissues with age and disease.

Untargeted lipidomics of ovine milk to analyse the influence of different diet regimens

In this work we report a lipidomics approach to study the effects of two diet systems on the composition of ovine milk. Milk from two groups of Sarda sheep grazing on 40% (P40) and 60% (P60) of pasture were analyzed by a UHPLC-QTOF-MS analytical platform and data submitted to multivariate statistical analysis. Pairwise partial least square discriminant analysis of the lipid profile of the data was carried out to classify samples and to find discriminant lipids. The two dietary groups were characterized by differences in triacylglycerols, phosphocholines and phosphatidylethanolamines levels. Discriminants of the P40 group were TG and PC containing in their backbone saturated medium chain FA thus suggesting greater de novo fatty synthesis in the mammary gland. On the other hand, the P60 group was characterized by TG and PC formed by unsaturated long chain FA originating from the diet or from lipid mobilization.

Fat specific adipose triglyceride lipase is necessary for iron-mediated lipolysis and lipid mobilization in response to negative energy balance

Maintenance of energy balance is essential for the overall health of an organism. In mammals, both negative and positive energy balance are associated with disease states. To maintain their energy balance within a defined homeostatic setpoint, mammals have evolved complex regulatory mechanisms that control energy intake and expenditure. Traditionally, studies have focused on understanding the role of macronutrient physiology in energy balance. In the present study, we examined the role of the essential micronutrient iron in regulating energy balance. Using a dietary model, we found that a short course of excess dietary iron caused a negative energy balance resulting in a severe whole body wasting phenotype. This disruption in energy balance was due to an iron dependent increase in energy expenditure caused by a heightened basal metabolic rate and activity level. Using a transgenic mouse model lacking adipose triglyceride lipase (ATGL) specifically in fat tissue, we found that to meet the increased energetic demands, dietary iron caused increased lipid utilization that required fat specific ATGL-mediated lipid mobilization and wasting of subcutaneous white adipose tissue deposits. When fed dietary iron, mice lacking fat-specific ATGL activity were protected from fat wasting, and developed a severe cachectic response that is necessary to meet the increased energetic demands caused by the dietary regimen. Our work highlights the multi-faceted role of iron regulation of organismal metabolism and provides a novel in vivo mechanism for micronutrient control of lipolysis that is necessary for regulating mammalian energy balance.

Redox Regulation of Lipid Mobilization in Adipose Tissues

Lipid mobilization in adipose tissues, which includes lipogenesis and lipolysis, is a paramount process in regulating systemic energy metabolism. Reactive oxygen and nitrogen species (ROS and RNS) are byproducts of cellular metabolism that exert signaling functions in several cellular processes, including lipolysis and lipogenesis. During lipolysis, the adipose tissue generates ROS and RNS and thus requires a robust antioxidant response to maintain tight regulation of redox signaling. This review will discuss the production of ROS and RNS within the adipose tissue, their role in regulating lipolysis and lipogenesis, and the implications of antioxidants on lipid mobilization.