A proteomic analysis of excreted and circulating proteins from obese patients following two different weight-loss strategies

Abstract

Bariatric surgery is the most successful therapeutic approach to weight loss, but how it leads to weight loss, and how it resolves obesity-related complications, including type-2 diabetes, are poorly understood. This study, comprising two groups of individuals, one on a low-calorie diet (n = 5) and one undergoing bariatric surgery (n = 7), used both targeted and untargeted proteomic approaches to determine changes in protein levels pre- and post-intervention (i.e. 3-6 months later). Changes were observed in both circulating and excreted proteins following weight loss. Targeted multiplexed biochip arrays measured 12 plasma peptides/proteins involved in metabolism and inflammation: C-peptide, ferritin, interleukin-6, interleukin-1 alpha, resistin, insulin, tumor necrosis factor alpha, leptin, plasminogen-activator inhibitor-1, adiponectin, cystatin C, and C-reactive protein. Following a low-calorie diet, plasma insulin and C-reactive protein levels were significantly reduced (P = 0.045 and P = 0.030, respectively); adiponectin increased and leptin decreased following surgery (P = 0.014 and P = 0.005, respectively). Untargeted proteomic analysis employing 2D difference in-gel electrophoresis (DIGE) showed 28 protein spots with ≥1.5-fold changes in expression following weight loss by a low-calorie diet; comparison of pre- and post-intervention urine samples from the bariatric surgery group showed changes in excretion of 110 protein spots. The combination of targeted protein analysis by multiplexed arrays and an exploratory (i.e. an unbiased or discovery) proteomic assessment of hundreds of proteins offers valuable insights into the mechanistic differences between alternative weight-loss strategies. This is a powerful hypothesis-generating approach to study complex, multifactorial syndromes such as obesity. The findings that arise from these studies can then be validated in targeted, hypothesis-directed investigations.

Reduction of IL‐6 gene expression in human adipose tissue after sleeve gastrectomy surgery

“…A few studies have shown a reduction in subcutaneous adipose tissue gene expression of IL‐6 six months after bariatric surgery . After bariatric surgery‐induced weight loss, systemic IL‐6 levels have been reported to be more variable: either reduced or unchanged . Differences in type of bariatric surgery, tissue source, patient age, and/or follow‐up duration may account for some of these inconsistencies.…”

Identification of Protein Changes in The Urine of Hypothyroid Patients Treated with Thyroxine Using Proteomics Approach

“…The increase in the albumin levels may reflect an increase in the uptake of the thyroid hormones, increased binding to prevent renal loss and in maintaining a balanced supply to the peripheral tissues during lowered thyroxine circulation as is seen in hypothyroidism. We and others have previously reported the presence of increased albumin in post bariatric surgery and in metabolic unhealthy obesity [26]. Hypothyroid patients also present with low grade chronic inflammation [27] and the increased spots relating to albumin along with AMBP levels 13 also point to increase APP response along with and increased oxidative stress in the hypothyroid state.…”

“…Albumin secretion in the urine, above 150 mg/dl, is considered pathological (proteinuria) and is reflective of different systemic diseases, such as hypertension, diabetes or more locally kidney diseases (for example: glomerulonephritis). Increased albumin in the proteome with no evidence of urinary microalbuminuria, has been documented in number of proteomic studies [5,26]. The increase in the albumin levels may reflect an increase in the uptake of the thyroid hormones, increased binding to prevent renal loss and in maintaining a balanced supply to the peripheral tissues during lowered thyroxine circulation as is seen in hypothyroidism.…”

Bariatric surgery and nonalcoholic fatty liver disease

“…The effect of bariatric surgery on IL-1α has not been widely studied. A statistically significant reduction has been reported on diet-led weight loss in morbidly obese patients [163], although this small study did not find a statistically significant reduction in IL-1α levels in patients undergoing bariatric surgery.…”