Larger organ size caused by obesity is a mechanism for higher cancer risk

Grant, Haley; Zhang, Yifan; Li, Lu; Wang, Yan; Kawamoto, Satomi; Pénisson, Sophie; Fouladi, Daniel Fadaei; Shayesteh, Shahab; Blanco, Alejandra; Ghandili, Saeed; Zinreich, Eva S.; Graves, Jefferson S.; Park, Seyoun; Kern, Scott E.; Hooper, Jody E.; Yuille, Alan; Fishman, Elliot K.; Chu, Linda C.; Tomasetti, Cristian

doi:10.1101/2020.07.27.223529

Cited by 3 publications

(3 citation statements)

References 44 publications

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“…The meanSD of the average increase in body weights, liver weights, and liver weight per body weights were 28.314%, 26.57.9% and 0.990.11%, respectively in these studies (96,129,141,(147)(148)(149). Linear increases in liver, pancreas and kidney in obesity were also more recently reported in humans (applying weighted linear regression) (150). In the study of Hall et al in dogs (151), although increases in cardiac output, GFR and renal blood flow were apparent in obese dogs, when divided by body weight at the end of the study, the differences in flows dissipated for cardiac output and renal blood flow, and GFR seemed to be lower in obese dogs.…”

Section: Does Obesity Affect Blood Flows To Liver and Kidney And/or Organ Weights?supporting

confidence: 74%

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

et al. 2022

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In many comparative trials examining the effects of adult obesity on pharmacokinetics of drugs, conclusions were made based on values that were either not adjusted to total body weight or adjusted to non-obese body mass (e.g., ideal or lean body weight). In many cases these values were higher in the obese subjects. We have reviewed the data from comparative human trials, and it is apparent that in examining clearance normalization to total body weight (as typically done in studies involving pediatric obese patients), the clearances are often reduced in the obese. We have also reviewed the results of experimental obese versus non-obese rodent models. Those studies have mostly found that the systemic exposures to the same dose per body weight are increased, with obesity-related decreases in clearance. Furthermore, the expression of a number of important drug metabolizing enzymes are reduced in the experimental obese state. There is also evidence that obesity causes increases in the measured mass of eliminating organs such as liver and kidney. Human clearance normalized to total body weight appears to better reflect the underlying changes reported in the expression of protein and functional activity of drug clearance mechanisms.

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Section: Does Obesity Affect Blood Flows To Liver and Kidney And/or Organ Weights?supporting

confidence: 74%

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

et al. 2022

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“…A better understanding of factors that affect BAC achieved after alcohol ingestion is critical to estimate exposure of the brain and other organs to alcohol and, in turn, the toxic effects of alcohol. The degree of adiposity and liver volume (which correlates positively with obesity; Grant et al, 2020) significantly impact the BAC experienced after alcohol administration (Kwo et al, 1998). In this study, we investigated the relationships between body composition and systemic AER using the alcohol clamp technique in women whose BMI ranged from normal weight to severe obesity.…”

Section: Discussionmentioning

confidence: 99%

Fat‐free mass accounts for most of the variance in alcohol elimination rate in women

Seyedsadjadi

Ramchandani

Plawecki

et al. 2023

Alcohol: Clinical and Experimental Research

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Background: Understanding how blood alcohol concentrations (BAC) achieved after drinking are determined is critical to predicting alcohol exposure to the brain and other organs and alcohol's effects. However, predicting end-organ exposures is challenging, as there is wide variation in BAC achieved after drinking a specified volume of alcohol. This variation is partly due to differences in body composition and alcohol elimination rates (AER), but there are limited data on how obesity affects AER. Here, we assess associations between obesity, fat-free mass (FFM), and AER in women and examine whether bariatric surgeries, which are linked to an increased risk of alcohol misuse, affect these associations.Methods: We analyzed data from three studies that used similar intravenous alcohol clamping procedures to estimate AER in 143 women (21 to 64 years old) with a wide range of body mass index (BMI; 18.5 to 48.4 kg/m 2 ). Body composition was measured in a subgroup using dual-energy X-ray absorptiometry (n = 42) or Bioimpedance (n = 60), and 19 of the women underwent bariatric surgery 2.1 ± 0.3 years before participation. We analyzed data using multiple linear regression analyses.Results: Obesity and older age were associated with a faster AER (BMI: r s = 0.70 and age: r s = 0.61, both p < 0.001). Compared to women with normal weight, AER was 52% faster (95% Confidence Interval: 42% to 61%) in women with obesity. However, BMI lost predictive value when adding fat-free mass (FFM) to the regression model. Age, FFM, and its interaction explained 72% of individual variance in AER (F (4, 97) = 64.3, p < 0.001). AER was faster in women with higher FFM, particularly women in the top tertile of age. After controlling for FFM and age, bariatric surgery was not associated with differences in AER (p = 0.74). Conclusions:Obesity is associated with a faster AER, but this association is mediated by an obesity-related increase in FFM, particularly in older women. Previous findings of a reduced alcohol clearance following bariatric surgery compared with prior to surgery are likely explained by a reduction in FFM post-surgery.

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“…The etiology for the latter is still obscure, although it is known that obesity is a state of low-grade inflammation, which COVID-19 pushes to extremes (with a characteristic “cytokine storm”[ 74 ]). Of note, obesity may lead not only to more adipose tissue accumulation but also to larger abdominal organ size[ 75 ]; we have speculated that larger abdominal organs may provide a larger tissue reservoir for the pervasive SARS-CoV-2 virus, since the latter has indeed been localized in abdominal organs[ 76 ].…”

Section: Sars-cov-2 and Obesity/met-sy/nafldmentioning

confidence: 99%

Polycystic ovary syndrome: Pathways and mechanisms for possible increased susceptibility to COVID-19

Ilias¹,

Goulas²,

Zabulienė

2021

WJCC

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In 75% of women with polycystic ovary syndrome (PCOS), insulin action is impaired. In obesity, visceral adipose tissue becomes dysfunctional: Chronic inflammation is favored over storage, contributing to the development of metabolic complications. PCOS, metabolic syndrome (MetSy) and non-alcoholic fatty liver disease (NAFLD) apparently share common pathogenic factors; these include abdominal adiposity, excess body weight and insulin resistance. Alterations in the gut microbiome have been noted in women with PCOS compared to controls; these may lead to deterioration of the intestinal barrier, increased gut mucosal permeability and immune system activation, hyperinsulinemia and glucose intolerance, which hamper normal ovarian function and follicular development (all being hallmarks of PCOS). It has been proposed that PCOS may entail higher susceptibility to coronavirus disease 2019 (COVID-19) via its associated comorbidities (NAFLD, obesity, MetSy and alterations in the gut microbiome). Studies have found an association between acute respiratory distress syndrome (seen in severe cases of COVID-19) and the intestinal microbiome. Furthermore, apparently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can gain entry to the gastrointestinal tract via locally-expressed angiotensin converting enzyme type 2 receptors. Excess body weight is associated with more severe COVID-19 and increased mortality. Although robust links between SARS-CoV-2 infection and PCOS/NAFLD/gut microbiome/metabolic consequences are yet to be confirmed, it seems that strategies for adapting the intestinal microbiome could help reduce the severity of COVID-19 in women with PCOS with or without NAFLD, MetSy or obesity.

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Larger organ size caused by obesity is a mechanism for higher cancer risk

Cited by 3 publications

References 44 publications

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

Piecing together human adult comparative pharmacokinetic trials and rodent studies: What happens to drug clearance in obesity?

Fat‐free mass accounts for most of the variance in alcohol elimination rate in women

Polycystic ovary syndrome: Pathways and mechanisms for possible increased susceptibility to COVID-19

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