DICER-driven regulation of lipid metabolism and macrophage-adipocyte crosstalk in partial lipodystrophy Andréa L. Rocha, Rhaissa Godoi, Tanes Imamura de Lima, Diogo de Moraes, Bruna Brasil Brandão, Antonio F.M. Pinto, Heloísa Antoniella Braz-de-Melo, Felipe Corrêa da Silva, Tiago Tomazini Gonçalves, Letícia de Souza Figueiredo, João Pedro Mazzi, Niedson Correia de Lima Junior, Safira Maria Leite Sousa, Josiane Erica Miyamoto, Luiz Osório Leiria, Jan-Wilhelm Kornfeld, Kelly Grace Magalhães, Pedro Manoel Moraes-Vieira, Alan Saghatelian, Marcelo A. Mori Biomedicine and Pharmacotherapy, 2026 Partial lipodystrophy is characterized by abnormal fat distribution, impaired thermogenesis, systemic inflammation, and diminished DICER1 expression in adipose tissue. Using adipocyte-specific Dicer1-deficient murine models to mimic lipodystrophy, we identified early metabolic and inflammatory alterations associated with the onset of partial lipodystrophy. DICER deficiency in adipocytes impaired lipid metabolism, leading to increased release of saturated lipids and triglycerides into the medium while reducing the biosynthesis of anti-inflammatory lipids. These changes promoted a pro-inflammatory environment by inducing macrophages to release IL-1β. In parallel, both adipocyte-autonomous DICER deficiency and the resulting inflammatory environment impaired adipocyte thermogenic capacity. Lipidomic analyses revealed reduced levels of docosahexaenoic acid (DHA) and other polyunsaturated fatty acids (PUFAs) in Dicer1-deficient adipocytes, accompanied by increased expression of genes encoding CYP450 enzymes linked to lipid degradation, and reduced DHA biosynthesis. Co-culture experiments confirmed that Dicer1-deficient adipocytes exacerbate macrophage-driven pro-inflammatory profile and thermogenic gene suppression. Notably, DHA supplementation mitigated the pro-inflammatory response triggered by conditioned media from Dicer1-deficient adipocytes. These findings reveal a critical role for adipocyte DICER in regulating lipid metabolism, macrophage-adipocyte interactions, and thermogenic function, offering new insights into molecular mechanisms driving metabolic dysfunction and chronic inflammation associated with partial lipodystrophy.
Beet (Beta vulgaris L.) stalk and leaf supplementation changes the glucose homeostasis and inflammatory markers in the liver of mice exposed to a high-fat diet Isabela Micheletti Lorizola, Josiane Érica Miyamoto, Ana Luiza Figueiredo Vieira, Beatriz Rocchetti Sumere, Rosângela Maria Neves Bezerra, Marcio Alberto Torsoni, Adriana Souza Torsoni, Mauricio Ariel Rostagno, Marciane Milanski, Caroline Dário Capitani Food Chemistry Molecular Sciences, 2021 Although beet stalks and leaves are not consumed and are usually discarded, they are an important source of bioactive flavonoids possessing antioxidant and anti-inflammatory activity. The aim of this study was to assess the effect of supplementation with beet stalks and leaves on metabolic parameters and glucose homeostasis in mice exposed to a high-fat diet. Six-week-old male Swiss mice were randomly divided into five experimental groups submitted to either standard diet (CT) or high-fat diet (HF), and HF-fed mice were subdivided into three treatment groups supplemented with oven-dehydrated beet stalks and leaves (SL), lyophilized beet stalks and leaves (Ly) or beet stalk and leaf extract (EX). Supplementation with SL promoted a mild improvement in the glucose homeostasis and decreased the protein levels of TNFα with no alterations in hepatic triglyceride content. It remains to be clarified if the enhancement in the glucose homeostasis observed in HFSL could be a consequence of improvement in pancreatic insulin secretion and/or glucose uptake from skeletal muscle and white adipose tissues.
Dietary Patterns Associated to Clinical Aspects in Crohn’s Disease Patients Marina Moreira de Castro, Ligiana Pires Corona, Lívia Bitencourt Pascoal, Josiane Érica Miyamoto, Leticia Martins Ignacio-Souza, Maria de Lourdes Setsuko Ayrizono, Marcio Alberto Torsoni, Adriana Souza Torsoni, Raquel Franco Leal, Marciane Milanski Scientific Reports, 2020 Diet is an important factor in both the pathogenesis and in the clinical course of Crohn’s disease (CD). However, data on dietary patterns of CD patients are rather limited in the literature. This cross-sectional study included 60 patients with CD, aged 18–60 years. Dietary intake was assessed using a validated food frequency questionnaire to measure food consumption patterns by principal component analysis (PCA). Multiple regression analysis was performed to investigate the association between dietary patterns and clinical and demographic variables. Three dietary patterns were identified: “Traditional + FODMAP” was associated with symptoms, gender, previous surgeries, and duration of the disease. “Fitness style” was positively associated with physical activity and negatively associated with body mass index and smoking. “Snacks and processed foods” was positively associated with duration of the disease and negatively associated with age. According to the weekly food consumption analysis, patients with active disease consumed less coffee and tea. We found significant associations between the three dietary patterns and the variables, but not with the stage of the disease. Prospective studies are necessary to determine the effects of food consumption patterns on the clinical course of CD.
Interesterified palm oil impairs glucose homeostasis and induces deleterious effects in liver of Swiss mice Josiane Érica Miyamoto, Andressa Reginato, Mariana Portovedo, Raísa Magno dos Santos, Marcella Aparecida Stahl, Hervé Le Stunff, Márcia Queiroz Latorraca, Marise Auxiliadora de Barros Reis, Vanessa Cristina Arantes, Diego Luiz Doneda, Leticia Martins Ignacio-Souza, Adriana Souza Torsoni, Renato Grimaldi, Ana Paula Badan Ribeiro, Marcio Alberto Torsoni, Marciane Milanski Metabolism Clinical and Experimental, 2020
Acute effects of fatty acids on autophagy in NPY neurones Andressa Reginato, Beatriz Piatezzi Siqueira, Josiane Érica Miyamoto, Mariana Portovedo, Suleyma de Oliveira Costa, Thaís Fante, Hosana Gomes Rodrigues, Letícia Martins Ignácio‐Souza, Márcio Alberto Torsoni, Adriana Souza Torsoni, Hervé Le Stunff, Denise D. Belsham, Marciane Milanski Journal of Neuroendocrinology, 2020 High‐fat diet (HFD) feeding is deleterious to hypothalamic tissue, leading to inflammation and lipotoxicity, as well as contributing to central insulin resistance. Autophagy is a process that restores cellular homeostasis by degrading malfunctioning organelles and proteins. Chronic HFD‐feeding down‐regulates hypothalamic autophagy. However, the effects of short‐term HFD‐feeding and the saturated fatty acid palmitate (PA) on hypothalamic autophagy and in neurones that express neuropeptide Y (NPY) and agouti‐related peptide remains unknown. Therefore, we assessed hypothalamic autophagy after 1 and 3 days of HFD‐feeding. We also injected PA i.c.v and analysed the modulation of autophagy in hypothalamic tissue. Both interventions resulted in changes in autophagy‐related gene profiles without significant differences in protein content of p62 and LC3B‐II, markers of the autophagy pathway. When we assessed native NPY neurones in brain slices from PA‐treated animals, we observed increased levels of Atg7 and LC3B protein in response to PA treatment, indicating the induction of autophagy. We then tested the direct effects of fatty acids using the immortalised hypothalamic NPY‐expressing neuronal cell model mHypoE‐46. We found that PA, but not palmitoleate (PO) (a monounsaturated fatty acid), was able to induce autophagy. Co‐treatment with PA and PO was able to block the PA‐mediated induction of autophagy, as assessed by flow cytometry. When the de novo ceramide synthesis pathway was blocked with myriocin pre‐treatment, we observed a decrease in PA‐mediated induction of autophagy, although there was no change with the toll‐like receptor 4 inhibitor, TAK‐242. Taken together, these findings provide evidence that saturated and unsaturated fatty acids can differentially regulate hypothalamic autophagy and that ceramide synthesis may be an important mediator of those effects. Understanding the mechanisms by which dietary fats affect autophagy in neurones involved in the control of energy homeostasis will provide potential new pathways for targeting and containing the obesity epidemic.