Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans

Ockenga, J.; Valentini, Luzia; Schuetz, T.; Wohlgemuth, Franziska; Glaeser, S; Omar, Ajmal; Kasim, E.; DuPlessis, Daniel; Featherstone, Karen; Davis, John R.; Tietge, Uwe J. F.; Kroencke, Thomas J.; Biebermann, Heike; Köhrle, Josef; Brabant, Georg

doi:10.1210/jc.2011-2329

Cited by 57 publications

(47 citation statements)

References 22 publications

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“…BAs increase energy expenditure (EE) in skeletal muscle and in brown adipose tissue (BAT) (151). The same holds true for postprandial thermogenesis, in particular; because BAT functions in the thermic effect of feeding and because postprandial levels of circulating BAs are strongly correlated with postprandial EE in lean individuals (102), it seems plausible that elevated BAs post-RYGB contribute to the increased postprandial EE.…”

Section: Bile Acidsmentioning

confidence: 99%

The physiology underlying Roux-en-Y gastric bypass: a status report

Lutz

Bueter

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Lutz TA, Bueter M. The physiology underlying Roux-en-Y gastric bypass: a status report. Am J Physiol Regul Integr Comp Physiol 307: R1275-R1291, 2014. First published September 24, 2014 doi:10.1152/ajpregu.00185.2014.-Obesity and its related comorbidities can be detrimental for the affected individual and challenge public health systems worldwide. Currently, the only available treatment options leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality are based on surgical interventions. This review will focus on two main clinical effects of Roux-en-Y gastric bypass (RYGB), namely body weight loss and change in eating behavior. Animal experiments designed to understand the underlying physiological mechanisms of these post-gastric bypass effects will be discussed. Where appropriate, reference will also be made to vertical sleeve gastrectomy. While caloric malabsorption and mechanical restriction seem not to be major factors in this respect, alterations in gut hormone levels are invariably found after RYGB. However, their causal role in RYGB effects on eating and body weight has recently been challenged. Other potential factors contributing to the RYGB effects include increased bile acid concentrations and an altered composition of gut microbiota. RYGB is further associated with remarkable changes in preference for different dietary components, such as a decrease in the preference for high fat or sugar. It needs to be noted, however, that in many cases, the question about the necessity of these alterations for the success of bariatric surgery procedures remains unanswered.Roux-en-Y gastric bypass; vertical sleeve gastrectomy; gut hormones; restriction; malabsorption; energy expenditure THE OBESITY EPIDEMIC AND ITS related comorbidities constitute a major challenge for both personal health and public health systems worldwide. The enormous increase in knowledge about the physiological mechanisms that control eating and body weight contrasts with the lack of available pharmacological therapies leading to safe, efficient, and long-lasting body weight reductions and amelioration of obesity-related comorbidities. However, recent insights into underlying mechanisms of obesity and bariatric surgery have led to promising perspectives in respect to gut hormone-based strategies against obesity. Nevertheless, best results for maintained weight reduction and improvement of comorbidities are still achieved by surgical means (22,88,121,135,136). This review aims to summarize key findings in respect to underlying physiological mechanisms of the Roux-en-Y gastric bypass (RYGB) procedure, which is the most commonly performed bariatric operation worldwide and thus, by many is considered as the gold standard in bariatric surgery. Sporadic reference will also be made to vertical sleeve gastrectomy (VSG) when appropriate. Both operations reduce eating at least temporarily (19,140,143) and lead to changes in food preferences (20,27,72). The majority of data collected with...

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Section: Bile Acidsmentioning

confidence: 99%

The physiology underlying Roux-en-Y gastric bypass: a status report

Lutz

Bueter

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Presumably, the ability of bile acids to increase energy expenditure is linked to a TGR5-mediated rise in cAMP, which results in augmented activation of D2 and thereby increased conversion of T 4 into T 3 in BAT (rodents) and muscle (humans) (11). However, human studies have yielded conflicting results (111,112,113 …”

Section: Bile Acids Activate Gpcrsmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

Sonne

Hansen

Knop

2014

European Journal of Endocrinology

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Bile acid sequestrants have been used for decades for the treatment of hypercholesterolaemia. Sequestering of bile acids in the intestinal lumen interrupts enterohepatic recirculation of bile acids, which initiate feedback mechanisms on the conversion of cholesterol into bile acids in the liver, thereby lowering cholesterol concentrations in the circulation. In the early 1990s, it was observed that bile acid sequestrants improved glycaemic control in patients with type 2 diabetes. Subsequently, several studies confirmed the finding and recently -despite elusive mechanisms of action -bile acid sequestrants have been approved in the USA for the treatment of type 2 diabetes. Nowadays, bile acids are no longer labelled as simple detergents necessary for lipid digestion and absorption, but are increasingly recognised as metabolic regulators. They are potent hormones, work as signalling molecules on nuclear receptors and G protein-coupled receptors and trigger a myriad of signalling pathways in many target organs. The most described and well-known receptors activated by bile acids are the farnesoid X receptor (nuclear receptor) and the G protein-coupled cell membrane receptor TGR5. Besides controlling bile acid metabolism, these receptors are implicated in lipid, glucose and energy metabolism. Interestingly, activation of TGR5 on enteroendocrine L cells has been suggested to affect secretion of incretin hormones, particularly glucagon-like peptide 1 (GLP1 (GCG)). This review discusses the role of bile acid sequestrants in the treatment of type 2 diabetes, the possible mechanism of action and the role of bile acid-induced secretion of GLP1 via activation of TGR5.

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“…However, these effects may be due to the modulation of intracellular pathways unrelated to TGR5 activation (Malisova et al 2013). In fact, thermogenic effects of BA were also verified in a human study by Ockenga et al (2012), who reported a positive association in subjects of venous BA concentrations with energy expenditure; however, this was not observed in obese subjects (Brufau et al 2010). The effect of BA on thyroid function seems to be more complex.…”

Section: Ba Thyroid Functions and Energy Expenditurementioning

confidence: 86%

“…The effect of BA on thyroid function seems to be more complex. A negative association between BA and TSH levels has been reported in certain patients (Patti et al 2009, Ockenga et al 2012 as well as in healthy subjects (Song et al 2015). This is most likely due to the effect of BA on TGR5 expressed in the pituitary gland (Doignon et al 2011, Ockenga et al 2012.…”

Section: Ba Thyroid Functions and Energy Expenditurementioning

confidence: 99%

The role of bile acids in metabolic regulation

Vı́tek¹,

Haluzı́k²

2016

Journal of Endocrinology

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Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA.

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Plasma Bile Acids Are Associated with Energy Expenditure and Thyroid Function in Humans

Abstract: Our data support a role of BA in human energy metabolism and in thyroid hormone control. Even though no convincing response to BA was demonstrated in TSHoma and TαT1 cells, the TSH decrease after a nutritional challenge suggests an interaction of BA on the set point of the thyroid axis.

Cited by 57 publications

References 22 publications

The physiology underlying Roux-en-Y gastric bypass: a status report

The physiology underlying Roux-en-Y gastric bypass: a status report

MECHANISMS IN ENDOCRINOLOGY: Bile acid sequestrants in type 2 diabetes: potential effects on GLP1 secretion

The role of bile acids in metabolic regulation

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