New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery

Angelini, Giulia; Castagneto-Gissey, Lidia; Corpo, Giulia Del; Giordano, Carla; Cerbelli, Bruna; Severino, Anna; Manco, Melania; Basso, Nicola; Birkenfeld, Andreas L.; Bornstein, Stefan R.; Genco, Alfredo; Mingrone, Geltrude; Casella, Giovanni

doi:10.1038/s41598-019-53702-4

Cited by 24 publications

(25 citation statements)

References 38 publications

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“…Hepatic AMPK and CPT1α transcripts were studied by RT PCR and were proven to be significantly decreased as compared to controls [ 201 ]. In accordance with these findings it was recently shown that NASH patients showed significantly reduced hepatic AMPK expression and Thr172 αAMPK phosphorylation [ 202 ]. Therefore, one hypothesis arising from available molecular evidence in humans suggests increasingly upregulated cellular DNL in early stages of NAFLD, with hepatic AMPK and fat oxidation capacity becoming initially increased in a compensatory manner.…”

Section: Dysregulation Of Hepatic Ampk In Humanssupporting

confidence: 78%

A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Loeffelholz

Coldewey

Birkenfeld

2021

Cells

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5′AMP-activated protein kinase (AMPK) is known as metabolic sensor in mammalian cells that becomes activated by an increasing adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio. The heterotrimeric AMPK protein comprises three subunits, each of which has multiple phosphorylation sites, playing an important role in the regulation of essential molecular pathways. By phosphorylation of downstream proteins and modulation of gene transcription AMPK functions as a master switch of energy homeostasis in tissues with high metabolic turnover, such as the liver, skeletal muscle, and adipose tissue. Regulation of AMPK under conditions of chronic caloric oversupply emerged as substantial research target to get deeper insight into the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Evidence supporting the role of AMPK in NAFLD is mainly derived from preclinical cell culture and animal studies. Dysbalanced de novo lipogenesis has been identified as one of the key processes in NAFLD pathogenesis. Thus, the scope of this review is to provide an integrative overview of evidence, in particular from clinical studies and human samples, on the role of AMPK in the regulation of primarily de novo lipogenesis in human NAFLD.

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Section: Dysregulation Of Hepatic Ampk In Humanssupporting

confidence: 78%

A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Loeffelholz

Coldewey

Birkenfeld

2021

Cells

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“…Our results also provided relevant information about the effects of metabolic surgery on adipose tissue dysfunction. Quantitative and qualitative changes in visceral and ectopic fat composition has been documented in magnetic resonance studies [ 9 , 24 , 25 , 26 ] and even molecular signatures of metabolic surgery have been recently described in the adipose tissue [ 27 ]. There would be then the opportunity for new adiposity-related biomarkers to emerge and address some of the current shortcomings in metabolic surgery.…”

Section: Discussionmentioning

confidence: 99%

Circulating Levels of Sclerostin Predict Glycemic Improvement after Sleeve Gastrectomy

et al. 2021

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Among the different effects of bariatric surgery, here we focus on bone-derived inflammatory molecules, and in particular, sclerostin; an osteocyte product potentially associated with cardio-metabolic diseases. In 94 morbidly obese patients undergoing laparoscopic sleeve gastrectomy (SG), over-time changes in anthropometric and biochemical measures—including insulin resistance (IR) indexes—were correlated with serum sclerostin levels. Sclerostin was positively associated with anthropometric indexes of obesity, and inversely with IR, namely homeostatic model assessment for peripheral insulin sensitivity (HOMA2%S) (r = −0.218; p = 0.045). Sclerostin emerged as the only significant predictor of HOMA2-%S normalization, independently of demographic and anthropometric variables (OR 1.01 (95% CI 1.00–1.02); p = 0.024). We also identified two distinct patterns of serum sclerostin change: the higher/lower sclerostin levels at baseline, the greater their post-surgical reduction/increase (p < 0.001 for all subgroups). Among those two patterns, especially the post-surgery increase in serum sclerostin was associated with lean mass reduction, without any association with IR indexes. Although counterintuitive, this change was likely dependent on the post-surgical increase in bone turnover. In conclusion, baseline serum levels of sclerostin correlate with anthropometric measures of obesity and IR, and the ability to predict glycemic improvements after SG. Specifically, serum sclerostin was closely associated with peripheral insulin sensitivity (HOMA2-%S), thus supporting the role of skeletal muscle/bone interactions in metabolic diseases.

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“…The improvement in insulin sensitivity after bariatric surgery is related to an improvement in plasma inflammatory biomarkers [112], as well as to a reduction in liver [114,115] and muscle fat accumulation [112,116], and to changes in subcutaneous adipose tissue histology with a consequent reduction of the adipocytes area and of the peri-adipocytes inflammation [112]. However, despite the large weight loss observed after surgery, insulin sensitivity does not completely normalize and sparse macrophages (mainly in T2D patients) are still present in SAT [112,117].…”

Section: Insulin Sensitivitymentioning

confidence: 99%

Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation

2021

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Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB—less after SG—bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.

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New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery

Cited by 24 publications

References 38 publications

A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

A Narrative Review on the Role of AMPK on De Novo Lipogenesis in Non-Alcoholic Fatty Liver Disease: Evidence from Human Studies

Circulating Levels of Sclerostin Predict Glycemic Improvement after Sleeve Gastrectomy

Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation

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