Increased blood levels of persistent organic pollutants (POP) in obese individuals after weight loss—A review

Jansen, A. A. J.; Lyche, Jan Ludvig; Polder, Anuschka; Aaseth, Jan; Skaug, Marit Aralt

doi:10.1080/10937404.2016.1246391

Cited by 58 publications

(28 citation statements)

References 110 publications

(163 reference statements)

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“…The finding that sucralose remains in the body for an extended period of time after termination of administration is consistent with exposure to other organochlorine compounds that exhibit long-term storage in adipose tissue (Jackson et al 2017). Adipose tissue is involved in a large number of metabolic and regulatory processes including endocrine functions (Greenberg and Obin 2006;Jansen et al 2017). Organochlorine compounds were found to modulate adipose tissue metabolism including increasing preadipocyte proliferation (Chapados et al 2012).…”

Section: Discussionsupporting

confidence: 53%

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

Bornemann¹,

Werness²,

Buslinger

et al. 2018

Journal of Toxicology and Environmental Health, Part A

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The aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 53%

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

Bornemann¹,

Werness²,

Buslinger

et al. 2018

Journal of Toxicology and Environmental Health, Part A

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“…The release of POPs also occurs during intentional weight loss. The amount released from adipose tissue during intentional weight loss is proportional to the magnitude of weight loss . Thus, the unexpected findings regarding cognition in the Look AHEAD study could have been the result of the long‐term negative effects of POPs released from adipose tissue, despite many short‐term benefits (Figure 1).…”

Section: New Hypothesismentioning

confidence: 99%

“…The amount released from adipose tissue during intentional weight loss is proportional to the magnitude of weight loss. 36 Thus, the unexpected findings regarding cognition in the Look AHEAD study could have been the result of the long-term negative effects of POPs released from adipose tissue, despite many short-term benefits (Figure 1). These negative effects would be at least as large as the short-term benefits of increased physical activity and improvements in traditional CVD risk factors.…”

Section: Lipophilic Chemical Mixtures As Neurotoxinsmentioning

confidence: 99%

Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study

Lee

Park

Lee

2020

Alzheimer's & Dementia

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Objective The aim of this paper is to propose a new hypothesis for the role of lipophilic chemical mixtures stored in adipose tissue in the development of dementia. Specifically, we present how the dynamics of these chemicals can explain the unexpected findings from the Action for Health in Diabetes (Look AHEAD) study, which failed to show long‐term benefits of intentional weight loss on cognition, despite substantial improvements in many known risk factors for dementia. Moreover, we discuss how the role of obesity in the risk of dementia can change depending on the dynamics of these chemicals in adipose tissue. New hypothesis Human adipose tissue is widely contaminated with various neurotoxic chemicals. Typical examples are persistent organic pollutants (POPs), strong lipophilic chemicals with long half‐lives. Both unintentional and intentional weight loss increases the release of POPs from adipocytes into the circulation. As POPs in the blood can easily reach the brain, the intentional weight‐loss group of the Look AHEAD study may have experienced an unappreciated and long‐term disadvantage on their cognition. Additionally, POPs may be involved in the link between obesity and dementia, as dysfunctional hypertrophic adipocytes enhance the release of POPs from adipocytes to the circulation through uncontrolled lipolysis. In contrast, metabolically healthy obese people may have a low risk of dementia because the safe storage of POPs in adipose tissue would decrease the amount of POPs reaching the brain. Major challenges for the hypothesis In human studies, there are practical difficulties involved with measuring POPs in the blood, including high costs and complex assays. As the serum concentrations of POPs are continuously affected by weight loss and gain, prospective studies may require serial measurements of POPs. In in‐vitro and in‐vivo experimental studies, how to simulate the exposure dose, duration, and mixture patterns in humans would be critical. Linkage to other major theories Even though POPs are direct neurotoxins at a high dosage, low‐dose POPs are mitochondrial toxins. Therefore, chronic exposure to low‐dose POPs is linked to known key interrelated mechanisms in the pathogenesis of dementia, such as mitochondrial dysfunction and neuroinflammation.

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“…During weight loss, whether intentional or unintentional, POPs are released from adipocytes to the circulation, resulting in increased amounts reaching other organs. [ 22 ] The increase in serum POP levels after intentional weight loss is proportional to the magnitude of weight loss. [ 22 ] On the contrary, weight gain can decrease serum POP levels by sequestration of POPs in adipocytes.…”

Section: What Happens With Lipophilic Persistent Organic Pollutants Smentioning

confidence: 99%

“…[ 22 ] The increase in serum POP levels after intentional weight loss is proportional to the magnitude of weight loss. [ 22 ] On the contrary, weight gain can decrease serum POP levels by sequestration of POPs in adipocytes. [ 23 ] Redistribution of POPs among organs during weight change was clearly demonstrated in an animal experimental study, in which weight loss led to redistribution of hexachlorobenzene, a POP, from adipose tissue to critical organs such as the brain.…”

Section: What Happens With Lipophilic Persistent Organic Pollutants Smentioning

confidence: 99%

Lipophilic Environmental Chemical Mixtures Released During Weight‐Loss: The Need to Consider Dynamics

et al. 2020

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Intentional weight loss can increase health risk in the long‐term, despite short‐term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs.

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Increased blood levels of persistent organic pollutants (POP) in obese individuals after weight loss—A review

Cited by 58 publications

References 110 publications

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study

Lipophilic Environmental Chemical Mixtures Released During Weight‐Loss: The Need to Consider Dynamics

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