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Melatonin is a pineal hormone that has acquired several unique modes of regulating the physiological effects in mammals due to its characteristic phylogenetic history. While melatonin exhibits immediate nocturnal effects, it also has next-day prospective effects that take place in the absence of this hormone. Besides that, the daily repetition and the annual variation in the duration of its synthesis determine its circadian and seasonal effects that characterize melatonin as a chronobiotic, a molecule that encodes time to the internal environment. Additionally, it presents transgenerational effects that are important for fetal programming, leading to a balanced energy metabolism in the adult life.Physiology, pathophysiology and therapeutic value of melatonin in metabolism and metabolic disorders.The typical mechanisms of action of melatonin (immediate, prospective, chronobiotic and transgenerational) should be considered to adequately understand its physiological effects on the regulation of metabolism in humans and, as a result, to understand the metabolic pathophysiological consequences caused by its synthesis and/or signaling disturbances. That points to the importance of a broader understanding of melatonin actions, besides the classical endocrinological point of view, that would allow the clinician/research to proper interpret its role in health maintenance.

FAPESP Background: We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. Methods: For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 mu M. The following parameters were evaluated:lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Results: Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. Conclusions: Palmitoleic acid, by concerted action on lipolysis, Gamma A esterification, mitochondrial Gamma A oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone. Univ Fed Sao Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, 210 Sao Nicolau St, BR-09913030 Diadema, Brazil Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, Brazil Cruzeiro do Sul Univ, Inst Phys Act Sci & Sports, Interdisciplinary Postgrad Program Hlth Sci, Sao Paulo, Brazil Univ Fed Espirito Santo, Hlth Sci Ctr, Dept Nursing, Vitoria, Spain Univ Fed Sao Paulo, Inst Environm Sci Chem & Pharmaceut, Dept Biol Sci, 210 Sao Nicolau St, BR-09913030 Diadema, Brazil FAPESP: 2011/51627-8 FAPESP: 2011/51701-3 Web of Science

Previous studies have demonstrated that long chain fatty acids influence fibroblast function at sub-lethal concentrations. This study is the first to assess the effects of oleic, linoleic or palmitic acids on protein expression of fibroblasts, as determined by standard proteomic techniques. The fatty acids were not cytotoxic at the concentration used in this work as assessed by membrane integrity, DNA fragmentation and the MTT assay but significantly increased cell proliferation. Subsequently, a proteomic analysis was performed using two dimensional difference gel electrophoresis (2D-DIGE) and MS based identification. Cells treated with 50 μM oleic, linoleic or palmitic acid for 24 h were associated with 24, 22, 16 spots differentially expressed, respectively. Among the identified proteins, α-enolase and far upstream element binding protein 1 (FBP-1) are of importance due to their function in fibroblast-associated diseases. However, modulation of α-enolase and FBP-1 expression by fatty acids was not validated by the Western blot technique.