Chair: Joanna H. Śliwowska (University of Life Sciences, Poznan, Poland) and Monika Kaczmarek (Institute of Animal Reproduction and Food Research, Olsztyn, Poland)

Symposium 9: Brain and metabolism

Obesity and diabetes have become the critical medical and economic challenges. Advances in the field, with emphasis on both prenatal and postnatal effects of over- and undernutrition on brain outcomes, will be presented. Potential mechanisms responsible for the above alterations, as well as advances in treatment, will be discussed.


Prof. Silvia Giatti, University of Aberdeen, Aberdeen, UK

Diabetic encephalopathy in preclinical models of diabetes mellitus: which role for neuroactive steroids?

Patients with diabetes mellitus (DM) often experience diabetic encephalopathy, leading to a higher risk of cognitive decline, dementia, and Alzheimer’s disease, though the exact mechanisms remain still elusive1. Compelling data, obtained both in clinical settings and in animal models of DM, indicates that cognitive impairment may result from multiple contributing factors, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and abnormal synaptic formation. This pathological state also disrupts neuroactive steroid levels in both plasma and the brain. These steroids are crucial regulators of neural function and have demonstrated neuroprotective effects in various neuropathological conditions2. This presentation will cover findings from preclinical models of DM on this subject.

References:
1. Riederer P, et al. The diabetic brain and cognition. J. Neural. Transm., 2017. doi: 10.1007/s00702-017-1763-2
2. Melcangi R.C., Giatti, S., Garcia-Segura, L.M. Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features. Neurosci. Biobehav. Rev., 2016. doi: 10.1016/j.neubiorev.2015.09.023


Prof. Monika Kaczmarek, Institute of Animal Reproduction and Food Research, PAS, Olsztyn, Poland

Lactocrine-based mechanisms responsible for reprogramming of reproductive fitness over generations

Environmental factors shape the developmental trajectories of organisms and influence overall physiological well-being. Maternal diet deficits can significantly impact offspring health, including reproductive fitness. Our research explores lactocrine-based mechanisms that program reproductive fitness across generations by studying key signaling pathways, including the CNS, gonads, gamets, and peripheral factors, such as leptin. We found that transient undernutrition during the early postnatal period led to sex-specific neuroendocrine responses affecting reproduction in two generations. This not only influenced the timing of puberty but also altered the hormonal and molecular environments of the hypothalamic pituitary-gonadal axis, ultimately impacting reproductive efficacy in both males and females. Our findings emphasize the role of parental nutritional history in shaping the developmental paths of future generations, with early-life impacts.

References:
1. https://pubmed.ncbi.nlm.nih.gov/27146259/
2. Results of current project (publications under under review/in preparation – https://projekty.ncn.gov.pl/opisy/432953-en.pdf)


Prof. Paloma Collado, Universidad Nacional de Educación a Distancia, UNED, Madrid, Spain

Hormonal modulation during development of the effects of malnutrition

The early stages of life are crucial for the development of the neurohormonal systems that regulate feeding. Hormones such as leptin or ghrelin are involved in the programming of the hypothalamic feeding circuit. Studies carried out by our group have shown that the presence of gonadal steroids during the first postnatal weeks is also necessary both for the programming of the energy metabolism and feeding circuits and for the modulation of the alterations produced by the intake of high-fat or low-protein diets from the early stages of gestation and during development. In addition, these programming and modulating functions are sexually differentiated in males and females and depend on the hormone considered1,2.

References:
1. Carrillo B, et al. Blocking of estradiol receptors ERα, ERβ and GPER during development differentially alters energy metabolism in male and female rats. Neuroscience., 2020. doi: 10.1016/j.neuroscience.2019.11.008
2. Carrillo B, et al. Physiological and brain alterations produced by high fat diet in male and female rats can be modulated by increased levels of estradiol during critical periods of development. Nutr.Neurosci., 2019. doi: 10.1080/1028415X.2017.1349574


Prof. Joanna H. Śliwowska, Poznan University of Life Sciences, Poznań, Poland

How prenatal exposure to cafeteria diet, which leads to obesity affect the reproduction?

Environmental factors, such as diet, influence the development and health outcomes of offspring. The maternal overnutrition via access to cafeteria (CAF) diet in animals, which mimics the Western diet consumed by humans, can reprogram endocrine systems, leading to various diseases, including metabolic and reproductive ones. Our research explores mechanisms via which the CAF diet alters metabolic and reproductive outcomes, emphasizing sex differences. We have found that CAF material diet affects body weight and composition in offspring, alters metabolic profiles, and leads to inflammation and delayed puberty in female offspring. Moreover, we have found that the above changes are sex-specific and occur in the Kiss1/Gpr54 and Sirt1 systems in the brain and liver in the offspring. Thus, we have concluded that the mother’s CAF diet leads to sex-specific alterations in metabolic and reproductive outcomes via the Kiss1/Gpr54 and Sirt1 systems in offspring. Together, our findings underline the role of maternal overnutrition on development and later life periods, especially in terms of metabolism and reproduction.

References:
1. https://pubmed.ncbi.nlm.nih.gov/37665248/; https://pubmed.ncbi.nlm.nih.gov/34535697/

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