How Does The Brain Create Our Perception Of Reality?

SHR # 2805 :: Is This Why Post-Menopausal Women Have A Hard Time Losing Weight?

: Carl Lanore; 20 December 2021; 03 February 2022

Guest: Dr. Holly A. Ingraham Ph.D.

Estrogen depletion in rodents and humans leads to inactivity, fat accumulation and type 2 diabetes, underscoring the conserved metabolic benefits of estrogen that inevitably decrease with age. In rodents, the pre-ovulatory surge in 17β-estradiol (E2) temporarily increases energy expenditure to coordinate increased physical activity with peak sexual receptivity. Here we report that a subset of estrogen-sensitive neurons in the ventrolateral ventromedial hypothalamic nucleus projects to arousal centers in the hippocampus and hindbrain, and enables estrogen to rebalance energy allocation in female mice.

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Holly A. Ingraham, Ph.D.,
is the Herzstein Professor of Molecular Physiology at the University of California. She studies women's health, in particular, sex-dependent central regulation of female metabolism and physiology. She was Elected to the American Association for the Advancement of Science in 2012, the American Academy of Arts and Sciences in 2019, and the National Academy of Sciences in 2021.

Associated Study: Oestrogen engages brain MC4R signalling to drive physical activity in female mice

"Mouse study identifies specific neurons and a signaling pathway to regions of the hindbrain that mediate sexual reproductive activity and physical activity that appear to influence activity behaviors during ovulation. The findings may provide valuable insights into how estrogen loss during menopause disrupts this activity."

Show Notes / Time Stamps

[03:38] - Why this research
[03:55] - How the hypothalamus develops
[05:06] - How estrogen and neurons in the hypothalamus affect energy expenditure
[05:34] - Weight gain and visceral fat
[06:07] - Understanding how to manipulate pathways and circumvent the use of estrogen and HRT
[10:30] - Activating those neurons artificially got mice to move
[11:13] - What’s the molecular signature of these neurons that motivate this activity
[12:03] - These neurons control spontaneous movement, and it's all linked to estrogen
[14:05] - Estrogen is triggering the expression of this signaling system
[14:43] - The melanocortin system may be one of the most important hormonal systems
[18:43] - Oxytocin changes the microbiome
[18:58] - Women have more irritable bowel syndrome, visceral pain
[19:11] - Estrogen in the proximal colon
[21:17] - The mice did not lose weight
[22:15] - Bone density in those mice went up 10%
[23:36] - German farmers measured the activity of cows to identify when to breed
[24:02] - Athletes’ peak performance is usually in the follicular phase B as estrogen is increasing
[36:10] - 200 years ago the average life expectancy wouldn’t exceed menopause
[36:25] - Now we're living at least three decades without estrogen
[40:41] - Looking into selective estrogen modulators
[41:37] - Specialized drug delivery
[52:23] - Movement is the most important ingredient for longevity
[55:09] - In post-menopause distribution of fat changes from subcutaneous to visceral
[56:13] - Hormones have powerful effects on metabolism and the brain
[59:17] - Testosterone for women is converted to estrogen
[59:35] - The right dose to eliminate the symptoms and make you feel like moving
[1:00:] - This research is to take a detailed relook at HRT for women