Clarissa Menezes Maya-Monteiro1,2,3, Felipe Corrêa-da-Silva4, Susanna S Hofmann5, Matthijs K C Hesselink6, Susanne E la Fleur4,7, Chun-Xia Yi4. 1. Laboratory of Immunopharmacology, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil, clarissamayam@gmail.com. 2. Laboratory of Endocrinology and Department of Endocrinology and Metabolism, Amsterdam Neuroscience, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, The Netherlands, clarissamayam@gmail.com. 3. Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands, clarissamayam@gmail.com. 4. Laboratory of Endocrinology and Department of Endocrinology and Metabolism, Amsterdam Neuroscience, Amsterdam University Medical Centers (UMC), University of Amsterdam, Amsterdam, The Netherlands. 5. Institute for Diabetes and Regeneration, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany. 6. Department of Nutrition and Movement Sciences, Maastricht University Medical Centre+ and NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht, The Netherlands. 7. Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
Abstract
BACKGROUND: In peripheral tissues, the lipid droplet (LD) organelle links lipid metabolism, inflammation, and insulin resistance. Little is known about the brain LDs. OBJECTIVES: We hypothesized that hypothalamic LDs would be altered in metabolic diseases. METHODS: We used immunofluorescence labeling of the specific LD protein, PLIN2, as the approach to visualize and quantify LDs. RESULTS: LDs were abundant in the hypothalamic third ventricle wall layer with similar heterogeneous distributions between control mice and humans. The LD content was enhanced by high-fat diet (HFD) in both wild-type and in low-density lipoprotein receptor deficient (Ldlr -/- HFD) mice. Strikingly, we observed a lower LD amount in type 2 diabetes mellitus (T2DM) patients when compared with non-T2DM patients. CONCLUSIONS: LDs accumulate in the normal hypothalamus, with similar distributions in human and mouse. Moreover, metabolic diseases differently modify LD content in mouse and human. Our results suggest that hypothalamic LD accumulation is an important target to the study of metabolism.
BACKGROUND: In peripheral tissues, the lipid droplet (LD) organelle links lipid metabolism, inflammation, and insulin resistance. Little is known about the brain LDs. OBJECTIVES: We hypothesized that hypothalamic LDs would be altered in metabolic diseases. METHODS: We used immunofluorescence labeling of the specific LD protein, PLIN2, as the approach to visualize and quantify LDs. RESULTS: LDs were abundant in the hypothalamic third ventricle wall layer with similar heterogeneous distributions between control mice and humans. The LD content was enhanced by high-fat diet (HFD) in both wild-type and in low-density lipoprotein receptor deficient (Ldlr -/- HFD) mice. Strikingly, we observed a lower LD amount in type 2 diabetes mellitus (T2DM) patients when compared with non-T2DM patients. CONCLUSIONS: LDs accumulate in the normal hypothalamus, with similar distributions in human and mouse. Moreover, metabolic diseases differently modify LD content in mouse and human. Our results suggest that hypothalamic LD accumulation is an important target to the study of metabolism.