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IMPACT OF THE PERINATAL EXPOSURE TO ENVIRONMENTAL POLLUTANTS IN THE GENESIS OF OBESITY AND TYPE 2 DIABETES MELLITUS: METABOLIC AND EPIGENETIC ASPECTS

Abstract

Exposure to air pollution has been highlighted as an important risk factor for morbidity and mortality in the world. Several pollutants, such as particulate matter weighing d 2.5 ¼m (MP2.5), as well as one of its chemical compounds, 1,2-naphthoquinone (1,2-NQ), obtained by burning diesel, have been associated with the genesis of chronic diseases, including type 2 diabetes mellitus (T2D). It is known that the perinatal environment has a permanent impact on the formation of tissue structure and metabolism. However, it has not yet been demonstrated by, which molecular and epigenetic mechanisms, early exposure to pollutants, could be determinant for the genesis of obesity and T2D. Thus, the aims of the present study are to investigate: 1) changes in body weight, body composition (DEXA), food intake, energy expenditure (CLAMS), fasting glycemia, insulinemia, leptinemia, glucose and insulin tolerance, pyruvate tolerance. In addition, to evaluate by flow cytometry the serum and adipose levels of cytokines, the number and phenotype of macrophages in the epididymal adipose tissue and in the washed peritoneal cavity; 2) the anorexigenic effect and intracellular signaling in the hypothalamus in response to leptin and insulin in the offspring (8 and 15 weeks of age) whose mothers will be exposed to 1,2-NQ or MP2,5 or filtrated air (FA) during the perinatal period. If changes in the anorectic response to these hormones are observed, the protein expression of SOCS-3, PTP1B and TCPTP will be investigated in the hypothalamus of the offspring as possible mechanisms of resistance to these hormones; As aim 3) to investigate the DNA methylation levels, histone and gene expression modification of NPY (neuropeptide Y), AgRP (agouti-related-protein), POMC (proopimelanocortin), TRH and CRHR1 (corticotrophin releasing hormone receptor 1) in the hypothalamus; Prmd16 (PR domain containing 16) and UCP1 (uncoupling protein 1) in white and brown adipose tissue and Pdx1 (pancreatic and duodenal homeobox 1), insulin and Ngn3 (neurogenin 3) in the pancreas of the offspring (8 weeks of age) whose mothers were exposed to 1,2-NQ or MP2.5 or FA during the perinatal period. Finally, the aim 4) to investigate the DNA methylation levels, histone gene expression modification in the serum of females (exposed and non-exposed) before and after gestation for future comparison with the profile of the pups. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CAMPOLIM, CLARA MACHADO; WEISSMANN, LAIS; DE OLIVEIRA FERREIRA, CLILTON KRAUESS; ZORDAO, OLIVIA PIZETTA; SEGANTINE DORNELLAS, ANA PAULA; DE CASTRO, GISELE; ZANOTTO, TAMIRES MARQUES; BOICO, VITOR FERREIRA; FERNANDES QUARESMA, PAULA GABRIELE; ATAIDE LIMA, RAQUEL PATRICIA; DONATO, JOSE; VERAS, MARIANA MATERA; NASCIMENTO SALDIVA, PAULO HILARIO; KIM, YOUNG-BUM; PRADA, PATRICIA OLIVEIRA. Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice. SCIENTIFIC REPORTS, v. 10, n. 1 JUN 23 2020. Web of Science Citations: 0.
FURIGO, ISADORA C.; DE SOUZA, GABRIEL O.; TEIXEIRA, PRYSCILA D. S.; GUADAGNINI, DIOZE; FRAZAO, RENATA; LIST, EDWARD O.; KOPCHICK, JOHN J.; PRADA, PATRICIA O.; DONATO, JR., JOSE. Growth hormone enhances the recovery of hypoglycemia via ventromedial hypothalamic neurons. FASEB JOURNAL, v. 33, n. 11, p. 11909-11924, NOV 2019. Web of Science Citations: 2.
ABBOUD, KAHLILE YOUSSEF; REIS, SABRINA KAREN; MARTELLI, MARIA EDUARDA; ZORDAO, OLIVIA PIZETTA; TANNIHAO, FABIANA; DE SOUZA, ALESSANDRA ZANIN ZAMBOM; ASSALIN, HELOISA BALAN; GUADAGNINI, DIOZE; ROCHA, GUILHERME ZWEIG; SAAD, MARIO JOSE ABDALLA; PRADA, PATRICIA OLIVEIRA. Oral Glutamine Supplementation Reduces Obesity, Pro-Inflammatory Markers, and Improves Insulin Sensitivity in DIO Wistar Rats and Reduces Waist Circumference in Overweight and Obese Humans. NUTRIENTS, v. 11, n. 3 MAR 1 2019. Web of Science Citations: 2.

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