Adipose tissue (AT): energy storage, estrogen source, and inflammation source

AT (or fat tissue) gives women a reserve of energy to bear children, nurse them, work physically for long hours, and (throughout most of human history) migrate over vast distances. In a healthy premenopausal woman, subcutaneous fat is mainly stored in the hips, thighs, breasts and upper arms. Lesser amounts of AT are stored in the core of the healthy female body around the intestine, where it is called central adipose (CA), visceral adipose or trunk adipose (TA). Excess energy from food  is either “burned” as fuel for heat and used for energy and structure, or stored in adipose tissue.

The menopausal transition changes fat storage. Women in the menopausal transition can typically gain 10 – 15 pounds, mostly in the form of central adipose (CA) because of the menopausal transition loss of ovarian estrogen (aka estradiol), but also due to decreased physical activity and insomnia. [26][27][28]

Download

Some people have a higher metabolic rate (high metabolism), meaning they readily burn excess food energy rather than storing it. Others have a low metabolism and tend to store food energy as AT. People with high metabolic rates have more tiny organelles called mitochondria inside their AT cells, which converts food energy into metabolic energy and heat. For most peri- and postmenopausal women, metabolic rates lower and this changes their fat storage. [29][30]

There are 2 types of AT cells: brown (BAT) and white (WAT). BAT cells contain more mitochondria than WAT cells and are specialized to burn excess energy and generate heat. They contain many small fat droplets and don’t store much molecular fat. BAT have little impact on inflammation. WAT cells on the other hand, contain a single large fat droplet and few mitochondria and are the main type of cell in CA visceral fat. WAT is specialized for storing energy as fat.[31] WAT cells are also pro-inflammatory: they release signal molecules that cause the immune system to be overactive. WAT inhibits insulin signaling and promotes insulin resistance that in turn causes dysfunctional blood glucose regulation.[32]

Download

Estrogen can trigger the transformation of WAT into BAT, creating anti-inflammatory effects. Likewise, exercise improves adipose health by improving mitochondrial function and promoting the ‘browning’ of WAT and reducing inflammation. Thus exercise appears to mimic the effects of estrogen.[33]

Skeletal muscle: movement and bone strength

The muscle that contracts, relaxes, and moves your skeleton is a very large organ that stores energy in the form of a molecule called glycogen. Muscle is always remodeling itself in response to physical loads put on it. Muscle mass and muscle strength depend on balancing the creation and breakdown of muscle proteins, and this balance is controlled by both estrogen and exercise levels. [34] When muscle is not exercised, it loses strength and structure, a process called sarcopenia. [35][36]

The effects of estrogen on muscle strength in humans is understood mainly through the impact of lowering estrogen levels during the menopausal transition; muscle mass and strength decline quickly compared to muscle mass and strength in premenopausal women. Hormone therapy given to women to increase their estrogen to pre-menopausal levels was shown to increase the synthesis of muscle-contraction proteins, slowing the decline of muscle mass and strength. [37][38][39][40]

Exercise, including weight training, can reduce or compensate for the perimenopausal decline of muscle mass and strength. [41][42][43][44]

Adipose tissue and muscle communicate, or cross-talk, when CA sends pro-inflammatory signals. This leads to muscle degradation and dysfunctional muscle mitochondria. Inflamed muscle cells respond by sending out signals that feedback to the CA This spiral of physical aging effects is called “inflammaging”. [45][46]

Bio-chemical cross-talk also happens between muscle and bone. When exercised, skeletal muscle releases signaling molecules called myokines onto the bones where they attach.[47] Some myokine signaling stimulates bone building and reduces bone break-down. In response bone cells release signaling molecules called osteokines to muscle, which completes the feedback loop and helps to strengthen the muscle.

One type of myokine that interacts with adipose stimulates energy expenditure by AT, improves glucose tolerance, and reduces adiposity and inflammation. It is thought to be released from muscle tissue when it is stimulated with exercise. [48]  There is a specific myokine, called myostatin, that actually suppresses muscle and bone building, but its release can be suppressed by exercise. [49] It seems that myostatin levels are also sensitive to estrogen, which decreases the manufacture and release of myostatin in some muscle, thereby resulting in the building of more muscle. [50]

Bone: the dynamic human infrastructure

Bone, like muscle, is a dynamic tissue that is constantly remodeling in response to physical stresses placed on it. Bone is also a storage tissue, storing calcium and phosphorus needed in the rest of the body. Loss of ovarian estrogen during peri- and post- menopause can lead to irreparable bone break- down and fragility. [51][52]

Weight-bearing activity is necessary to keep bones strong and reduce low-impact fractures in perimenopausal and post-menopausal women. However there is conflicting scientific evidence about what types of exercise and movement are best for maintaining good bone strength. The best evidence to date suggests that weight-bearing activity, in particular weight lifting with lower repetitions and heavier weights, is the best activity for bone retention. [53] However, older bodies need gentler versions of most exercises, tailored to the fitness level and joint health of the individual – overly aggressive exercise can cause more harm than good. [54][55][56]

Hormone Therapy (HT) with estrogen clearly supports bone health in perimenopausal and post-menopausal women.[57][58][59] Estrogen supports bone health by decreasing bone resorption (bone break down and material recycling). Osteoblasts are bone cells that help retain bone structure by secreting a collagen matrix which becomes mineralized. Osteoblasts are sensitive to, and regulated by estrogen. The chemical signaling between estrogen and osteoblasts is complex and not fully understood. However, pro- inflammatory cytokines in the immune and adipose systems are suppressed by estrogen and in estrogen’s absence, bone resorption accelerates.[60]

Immune system: protects and defends the body from pathogens

The human immune system is very sensitive and responsive to the hormone estrogen.[61] (Taneja, 2018). Estrogen enhances the body’s ability to make antibodies and resist infection. A trade-off is that  disruptions of estrogen signaling, like menopausal transition, can trigger hyper-immune responses and autoimmune diseases in people genetically susceptible to them. (Desai and Brinton, 2019). Moderate levels of exercise are known to enhance immune system function and decrease systemic inflammation in mid- life and older women.[62] ( Brown, 2017).

The modulation of the immune system is very complex and not fully mapped. It isn’t understood how all of the signaling pathways sensitive to estrogen or physical exercise are brought together to impact the immune system. To date, we do know that a woman’s immune functions can be improved with consistent physical activity and training. Exercise remains critical to help improve symptoms of menopausal transition [63][64] (Brown, 2017).