Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation

Abstract

Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH–IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH–IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

Associations between Pre-Bariatric High-Sensitivity C-Reactive Protein and Post-Surgery Outcomes

“…A significant reduction in hs-CRP levels as early as 6 months after gastric bypass was evident in our patients. This reduction is in line with the results of previous studies [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ] which reported a reduction ranging from 29% [ 26 ] to around 90% [ 27 ] in the levels of CRP after bariatric surgery. A direct relationship between the degree of weight loss and CRP reduction was observed in several studies [ 20 , 24 ], but not all [ 51 ].…”

“…Bariatric surgery is reported to be effective both in the reduction of adipose tissue mass [ 13 , 14 ] and in the improvement of the obesity-associated co-morbidities, such as type 2 diabetes mellitus (T2DM), arterial hypertension, hyperlipidemia, obstructive sleep apnea [ 15 ], non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) [ 16 , 17 , 18 , 19 ]. Additionally, several studies have shown that bariatric surgery improved inflammatory status and reduced CRP values regardless of weight loss changes [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. This implies that interactions between a collection of factors can regulate inflammation.…”

Mechanistic Targets and Nutritionally Relevant Intervention Strategies to Break Obesity–Breast Cancer Links

“…This is supported by epidemiological studies that observed inverse relationships between physical activity and risks of BC ( 53 , 54 ). Interventions designed to reduce calorie intake, such as, calorie-restricted diets and intermittent fasting, can reverse the high levels of insulin and IGF-1 ( 55 – 57 ) ( Figure 1 ). However, there is no consensus regarding the impact of diet and exercise on IGF-1 and IGFPB.…”

“…Low circulating levels of IGF-1 were reached after 16 weeks of strength training ( 60 ). High levels of IGF-1 could be lowered temporarily by bariatric surgery ( 55 ); however, for long term reduction of IGF-1 level, a nutritional intervention is necessary to maximize the effects of the surgery on IGF-1 levels ( 55 , 61 ). Dietary interventions ( 55 – 57 ), in particular, a 2008 study by Fontana et al.…”

“…High levels of IGF-1 could be lowered temporarily by bariatric surgery ( 55 ); however, for long term reduction of IGF-1 level, a nutritional intervention is necessary to maximize the effects of the surgery on IGF-1 levels ( 55 , 61 ). Dietary interventions ( 55 – 57 ), in particular, a 2008 study by Fontana et al. demonstrated total caloric restriction (CR) and targeted protein reduction was needed to lower circulating serum IGF-1, albeit in a small study of six participants ( 56 ); however a recent meta-analysis of six clinical trials corroborated these findings in part, showing an increase in circulating IGF-1 in response to increased protein intake ( 57 ).…”