Endocrine implications of bariatric surgery: a review on the intersection between incretins, bone, and sex hormones

Abstract

Bariatric surgery is now the most widely used intervention for the treatment of human obesity. A large body of literature has demonstrated its efficacy in sustained weight loss and improvement in its associated comorbidities. Here, we review the effect of bariatric surgery in gut hormone physiology, bone remodeling and the reproductive axis. Rapid improvements in insulin release and sensitivity appear to be weight loss independent and occur immediately after surgery. These effects on pancreatic beta cells are mostly due to increased gut hormone secretion due to augmented nutrient delivery to the small intestine. Bone remodeling is also affected by gut hormones. Phenotypic skeletal changes observed in mice deficient in GLP-1 or GIP suggest that increased incretins may improve bone density. However, these positive effects may be counterbalanced by the association between weight loss and a reduction in bone density. Finally, studies have shown a marked improvement following bariatric surgery in infertility and PCOS in women and hypogonadism in men. Thus, the net effect on endocrine systems after bariatric surgery will likely vary on an individual basis and depend on factors such as comorbidities, peri-menopausal state, amount of weight loss, and likelihood to adhere to vitamin supplementation after surgery.

Keywords: Bariatric surgery; GLP-1; incretins; obesity.

Figure 1

Relationship between obesity, diabetes, inflammation, and bone health. Obesity is associated with insulin resistance and a pro‐inflammatory state that is associated with T2DM. In uncontrolled Type 1 and Type 2 diabetes several factors can worsen bone health; these include increased advanced glycation end products (AGEs) that result in osteoclast activation and osteoblast dysfunction leading to osteoporosis. Neuropathy, vision loss, and poor balance from prolonged poor glycemic control can increase fall risk, this coupled with increased bone fragility associated with Type 1 diabetes can further increase fracture risk.

Figure 2

The association between obesity, insulin resistance, and reproduction. Increased adiposity, in particular central obesity is associated with increased insulin resistance which leads to a reduction in sex hormone‐binding globulin (SHBG) production. This leads to a reduction in SHBG‐bound steroids such as total testosterone thereby resulting in an increase in free testosterone. In women, androgens are further increased by increased theca cell sensitivity which occurs in the setting of obesity and insulin resistance, a feature associated with PCOS. Androgen excess is a major cause of ovarian dysfunction and ovulatory disturbance that eventually leads to hypothalamic dysfunction in PCOS. In obese men, increased levels of free testosterone are converted to estrogen by aromatase in the setting of an abundance of adipose tissue, thus promoting inhibition of LH secretion by the pituitary which results in hypothalamic dysfunction. In both men and women, insulin resistance is associated with obstructive sleep apnea and increased inflammation which aggravate insulin resistance and perpetuate a hypogonadal state.

Figure 3

Combined effects after bariatric surgery on incretins, metabolic parameters, and bone health. Bariatric surgery is the most effective treatment for sustained weight loss in morbid obesity. The anatomical rearrangements lead to an increase in incretins which ultimately result in improved metabolic parameters associated with weight loss and improved insulin sensitivity.