Join Sharon Ladyman, PhD and Vicki Vieira-Potter, PhD as they present applications of rodent metabolic phenotyping with a focus on the effects of hormones and pregnancy on daily activity in mice.

A reduction in voluntary physical activity during pregnancy in mice is mediated by prolactin
Sharon Ladyman, PhD

Pregnancy is an energetically demanding challenge for the mother and as such, pregnant females undergo numerous metabolic adaptations to meet these demands, including increased food intake and a rapid lowering of energy expenditure and physical activity levels. A particularly striking example is a profound reduction in voluntary running wheel activity (RWA) that occurs as soon as mice become pregnant. We hypothesized that prolactin, one of the first hormones to increase in response to mating in rodents, drives the pregnancy-induced suppression of physical activity levels. We show that prolactin can acutely suppress RWA in virgin female mice but does not influence general locomotion. Conditional deletion of prolactin receptors (Prlr) from either all forebrain neurons or GABA neurons prevents the immediate pregnancy-induced suppression of RWA, and leads to higher RWA throughout pregnancy compared to controls. Furthermore, deletion of Prlr specifically from the medial preoptic area of the hypothalamus, a brain region associated with multiple homeostatic and behavioural roles including maternal behaviour, completely abolishes the early pregnancy-induced suppression of RWA. Our data demonstrate a key role for prolactin in suppressing voluntary physical activity during early pregnancy and highlights a biological basis for lower activity levels during pregnancy.

Neuronal and Metabolic Pathways Influenced by Sex Hormones
Vicki Vieira-Potter, PhD

Estrogen-sufficient females are more physically active than males and are protected against adipose tissue and systemic metabolic dysfunction. The mechanisms are not fully understood, but we demonstrate that ovarian removal causes significant mRNA changes in the nucleus accumbens (NAc) brain region (i.e., the reward center), which correlate significantly with physical inactivity. We hypothesize that sex differences in the NAc may help explain differences in physical activity and metabolism. Differentially expressed genes (DEG) in the NAc (RNAseq) in male and female C57BL6J mice were assessed and related to systemic metabolism (body composition via EchoMRI & body fat distribution; energy expenditure, sleep patterns, & running wheel activity via metabolic chambers; insulin resistance via surrogate measures; and adipose tissue metabolism via q-rtPCR. Females were more physically active with improved insulin sensitivity and adipose tissue mitochondrial metabolism. Top NAc DEGs were related to sexual development, immune regulation, obesity, and metabolism. Notably, functional over-enrichment analyses identified significant alterations in gene networks involved in the regulation of adipocyte metabolism (KEGG) and the circadian clock system (Panther). Overall, physical activity correlated strongly with Per3, a gene associated with circadian function, thermoregulation, and metabolism, which also correlated with adiposity. This study demonstrates that estrogen’s neural regulation of adipose tissue metabolism and physical activity may drive menopause-associated metabolic dysfunction.

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Senior Research Fellow
The University of Otago

Dr. Sharon Ladyman is a Senior Research Fellow in the Centre for Neuroendocrinology at the University of Otago, New Zealand. After two Postdoctoral Fellow positions in North America she returned to New Zealand and now has a senior position in Prof Dave Grattan’s laboratory group, which focuses on hormone-induced adaptations of the maternal brain. She leads studies investigating the neuroendocrine regulation of body weight, appetite and glucose homeostasis during pregnancy. Her work focuses on the neuro-hormonal circuits that mediate pregnancy-induced hyperphagia, suppression of physical activity and adaptive changes in thermoregulation during different reproductive states.

Associate Professor
University of Missouri

Dr. Vicki Vieira-Potter is an Associate Professor in the Department of Nutrition and Exercise Physiology at the University of Missouri, Columbia (MU). Her laboratory studies how estrogen loss affects energy metabolism and focuses on brain and adipose tissue-specific mechanisms. She and her team have demonstrated that aerobic fitness and exercise are protective against metabolic complications associated menopause; they use a variety of animal models and biomolecular techniques to address these research questions. She directs the Rodent Metabolic Phenotyping Core at MU. Dr. Vieira-Potter holds an undergraduate degree from Wheaton College (Norton, MA), and graduate degrees from the University of New Hampshire and the University of Illinois at Urbana Champaign, respectively. She completed postdoctoral training at the at Tufts (HNRCA) where she focused on obesity and metabolism. She has 70+ peer-reviewed publications in the area of adipose tissue/cardiometabolic disease. For complete details please review her complete publication list.

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Sable Systems International contributes to the research community with superior instrumentation and software for innovation and discovery. Their metabolic phenotyping systems measure calorimetry, respirometry, metabolic/behavioral phenotyping and gas analysis at the best possible resolution and precision, providing unprecedented analytical and statistical power.

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