Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients

Hankir, Mohammed K.; Rullmann, Michael; Seyfried, Florian; Preusser, Sven; Poppitz, S.; Heba, Stefanie; Gousias, Konstantinos; Hoyer, Jana; Schütz, Tatjana; Dietrich, Arne; Müller, Karsten; Pleger, Burkhard

doi:10.1172/jci.insight.131329

Cited by 13 publications

(20 citation statements)

References 73 publications

(111 reference statements)

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“…In this study, we found reduced levels of plasma LPS-binding protein (LBP), an acute phase protein that reflects systemic bacterial endotoxin levels [ 42 , 43 ] following RYGB treatment ( Figure 5 A), which is associated with decreased concentrations of circulating pro-inflammatory cytokines ( Figure 5 B). Similar changes in the peripheral inflammatory tone were recently reported in patients after RYGB surgery that were associated with reduced radiologic measures of hypothalamic inflammation [ 44 ]. Importantly, these changes in systemic low-grade inflammation and endotoxin levels were specific to RYGB-induced weight reduction, but were absent under chronic CR ( Figure 5 A and B).…”

Section: Resultssupporting

confidence: 81%

“…Weight-loss surgical procedures such as RYGB appear unique in their capacity to modulate central immune cell homeostasis despite ongoing access to a HFD. While direct and indirect evidence from rodent [ 57 ] and human studies [ 44 , 58 ] supports this concept, the mechanistic basis of how surgical gut rearrangements may control the central innate immune system interacting with neuronal appetite control remains unclear.…”

Section: Discussionmentioning

confidence: 99%

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Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk

Chen

Haase

Haange

et al. 2021

Molecular Metabolism

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Objective Hypothalamic inflammation and endoplasmic reticulum (ER) stress are extensively linked to leptin resistance and overnutrition-related diseases. Surgical intervention remains the most efficient long-term weight-loss strategy for morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigated whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signaling as a mechanistic account for post-operative appetite suppression. Methods RYGB or sham surgery was performed in high-fat diet-induced obese Wistar rats. Sham-operated rats were fed ad libitum or by weight matching to RYGB via calorie restriction (CR) before hypothalamic leptin signaling, microglia reactivity, and the inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signaling. Results RYGB, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signaling, and ER stress, which are linked to enhanced hypothalamic leptin signaling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the altered gut microbial environment upon RYGB surgery. Conclusions Our data demonstrate that RYGB interferes with hypothalamic TLR4 signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgical altered gut microbial environment.

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Section: Resultssupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk

Chen

Haase

Haange

et al. 2021

Molecular Metabolism

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“…For instance, a very recent study showed that Roux-en-Y gastric bypass surgery (a type of BS) progressively increased T 2 W signal intensities and decreased hypothalamic FA values, suggesting that this type of surgery has a time-dependent influence on the hypothalamic inflammation status. 26 Two other research groups, using T 1 -based images with VBM analysis, assessed the whole brain evolution after BS and found surgery-induced brain plasticity that could be observed not only in the hypothalamus, but also in hedonic control regions. 143,144 Moreover, these studies indicated that the higher BMI loss after surgery induced larger MRI-detected changes of grey and white matter densities across the entire brain.…”

Section: Future Perspectivesmentioning

confidence: 99%

“…24,25 Finally, yet importantly, a few clinical studies are beginning to implement neuroimaging methods to evaluate changes occurring in the brain during the recovery of weight-loss surgeries, including bariatric surgery (BS). 26 Typically, each imaging modality used focuses on a particular process – inflammation, metabolic or blood flow changes – but integrative studies providing a reproducible frame of results with unifying hypotheses and conclusions remain limited. In this sense, histochemical validations of the molecular, cellular or vascular events underlying the neuroimaging findings remain still necessary.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Lizarbe

Campillo

Guadilla

et al. 2020

J Cereb Blood Flow Metab

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Obesity is a current threat to health care systems, affecting approximately 13% of the world’s adult population, and over 18% children and adolescents. The rise of obesity is fuelled by inadequate life style habits, as consumption of diets rich in fats and sugars which promote, additionally, the development of associated comorbidities. Obesity results from a neuroendocrine imbalance in the cerebral mechanisms controlling food intake and energy expenditure, including the hypothalamus and the reward and motivational centres. Specifically, high-fat diets are known to trigger an early inflammatory response in the hypothalamus that precedes weight gain, is time-dependent, and eventually extends to the remaining appetite regulating regions in the brain. Multiple magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are currently available to characterize different features of cerebral obesity, including diffusion weighted, T2 and volumetric imaging and 1H and 13C spectroscopic evaluations. In particular, consistent evidences have revealed increased water diffusivity and T2 values, decreased grey matter volumes, and altered metabolic profiles and fluxes, in the brain of animal models and in obese humans. This review provides an integrative interpretation of the physio-pathological processes associated with obesity development in the brain, and the MRI and MRS methods implemented to characterize them.

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“…However, more studies found that modifications in metabolism and hormones played a greater role in fighting diabetes. In other words, bariatric surgery has the potential to treat diabetes by increasing the likelihood of insulin independency, improving incretin secretion, recovering islet function, and restoring peripheral insulin sensitivity to regulate glucose homeostasis [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Furthermore, bariatric surgery decreases circulating succinate levels [ 37 ] and curbs Krebs cycle completion to avoid excess glucose production, resulting in multiple metabolic improvements.…”

Section: Consequences Of Bariatric Surgerymentioning

confidence: 99%

Effect of Bariatric Surgery on Metabolic Diseases and Underlying Mechanisms

Lee

Kaura

et al. 2021

Biomolecules

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Obesity is a highly prevalent public health concern, attributed to multifactorial causes and limited in treatment options. Several comorbidities are closely associated with obesity such as the development of type 2 diabetes mellitus (T2DM), cardiovascular and cerebrovascular diseases, and nonalcoholic fatty liver disease (NAFLD). Bariatric surgery, which can be delivered in multiple forms, has been remarked as an effective treatment to decrease the prevalence of obesity and its associated comorbidities. The different types of bariatric surgery create a variety of new pathways for food to metabolize in the body and truncate the stomach’s caliber. As a result, only a small quantity of food is tolerated, and the body mass index noticeably decreases. This review describes the improvements of obesity and its comorbidities following bariatric surgery and their mechanism of improvement. Additionally, endocrine function improvements after bariatric surgery, which contributes to the patients’ health improvement, are described, including the role of glucagon-like peptide-1 (GLP-1), fibroblast growth factors 19 and 21 (FGF-19, FGF-21), and pancreatic peptide YY (PYY). Lastly, some of the complications of bariatric surgery, including osteoporosis, iron deficiency/anemia, and diarrhea, as well as their potential mechanisms, are described.

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Roux-en-Y gastric bypass surgery progressively alters radiologic measures of hypothalamic inflammation in obese patients

Cited by 13 publications

References 73 publications

Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk

Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk

Magnetic resonance assessment of the cerebral alterations associated with obesity development

Effect of Bariatric Surgery on Metabolic Diseases and Underlying Mechanisms

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