Epigenetic Transgenerational Inheritance of Obesity Susceptibility

King, Stephanie E.; Skinner, Michael K.

doi:10.1016/j.tem.2020.02.009

Cited by 105 publications

(83 citation statements)

References 142 publications

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“…Exposures of gestating females to endocrine‐disrupting compounds have been shown to affect adiposity in offspring of multiple generations, although it is unclear whether it is transmitted through the male germline, female germline, a combination of both germlines, or other mechanisms. [ 60,68 ] It has also been challenging to pinpoint the organ or cell type in the offspring as the major contributor to the metabolic phenotype. The current findings of the transgenerational effects of iAs through the exclusive male‐lineage transmission shed light on some of these issues and unveiled a few fascinating phenomena in the cross‐generational effects of environmental exposure on metabolism.…”

Section: Discussionmentioning

confidence: 99%

Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic

Gong

Xue

et al. 2021

Advanced Science

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The rise of metabolic disorders in modern times is mainly attributed to the environment. However, heritable effects of environmental chemicals on mammalian offsprings' metabolic health are unclear. Inorganic arsenic (iAs) is the top chemical on the Agency for Toxic Substances and Disease Registry priority list of hazardous substances. Here, we assess cross‐generational effects of iAs in an exclusive male‐lineage transmission paradigm. The exposure of male mice to 250 ppb iAs causes glucose intolerance and hepatic insulin resistance in F1 females, but not males, without affecting body weight. Hepatic expression of glucose metabolic genes, glucose output, and insulin signaling are disrupted in F1 females. Inhibition of the glucose 6‐phosphatase complex masks the intergenerational effect of iAs, demonstrating a causative role of hepatic glucose production. F2 offspring from grandpaternal iAs exposure show temporary growth retardation at an early age, which diminishes in adults. However, reduced adiposity persists into middle age and is associated with altered gut microbiome and increased brown adipose thermogenesis. In contrast, F3 offspring of the male‐lineage iAs exposure show increased adiposity, especially on a high‐calorie diet. These findings have unveiled sex‐ and generation‐specific heritable effects of iAs on metabolic physiology, which has broad implications in understanding gene‐environment interactions.

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Section: Discussionmentioning

confidence: 99%

Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic

Gong

Xue

et al. 2021

Advanced Science

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“…So we choose this animal model to develop our research. Obesity usually occurs due to excess nutrition and sedentary lifestyle ( 24 ), and fat tissue is essential for systemic metabolic homeostasis, and adipocytes can participate in regulating the body metabolism by increasing or decreasing the number or changing the size ( 25 ). Obesity can be effectively suppressed by inhibiting the differentiation of adipocytes or promoting the decomposition of adipocytes.…”

Section: Discussionmentioning

confidence: 99%

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

et al. 2021

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BackgroundPre-clinical research studies have shown that Madecassoside (MA) has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity.MethodsObese diabetic KKay/TaJcl mice model was adopted to the study. The body weight of all animals was recorded daily, and the blood glucose, blood lipid, and serum aminotransferase levels were examined, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat, and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1a, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR).ResultsThe results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα ↑, CPT1a↑, and PGC-1α↑). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat.ConclusionsTaken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.

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“…44 Given that this has happened in a short period of time relative to evolution of humans, genetic changes driven by selection pressures appear unable to explain this phenomenon although epigenetic factors may play a role. 8 Many factors that characterize the obesogenic environment have been recognized that increase risk of weight gain. These include sedentariness, 2 psychological stress, 4 sleep restriction, 5 medications, 10 consumption of energy dense foods, 6 along with exposure to marketing ploys that are inherently designed to influence consumer behavior in relation to food.…”

Section: Obesity As a Disease: Vulnerability To Weight Gainmentioning

confidence: 99%

“…The regulation of hunger and satiety is governed by a complex physiological system involving top down and bottom up feedback loops, which has the potential to become poorly regulated in today's obesogenic environment. 1 Here, a range of factors are conducive to weight gain that lead to risk of arriving at a pathological state of obesity: Sedentariness, 2 food culture impacting seasonal weigh gain, 3 stress, 4 poor sleep, 5 energy dense foods, 6 genetic/epigenetic factors, 7 epigenetic factors in response to the obesogenic environment that may potentially be transgenerational, 8 changes in gut microbiota, 9 and certain medications 10 increase the risk of weight gain and obesity along with other physiological and environmental cues. 11 Despite our growing understanding of the complexity and variety of precursors to deleterious weight gain, the stigma of obesity persists in popular culture, 12 the policy space, 13 and health care.…”

Section: Introductionmentioning

confidence: 99%

Obesity and responsibility: Is it time to rethink agency?

Grannell

Fallon²,

Al‐Najim

et al. 2021

Obesity Reviews

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Despite obesity declared a disease, there still exists considerable weight stigma in both popular culture and health care, which negatively impacts policy making regarding prevention and treatment. While viewed as a choice or a failure of willpower by many, evidence exists to challenge the argument that both weight gain and failure to achieve weight loss maintenance are the individuals' fault due to personal failure or lack of responsibility. In this article, we draw upon literature from obesity treatment, neuroscience, philosophy of mind, and weight stigma to challenge the commonly held beliefs that individuals are free to choose how much they can weigh, and achievement of long-term weight loss maintenance is completely subject to conscious choice. In reality, the regulation of hunger, satiety, energy balance, and body weight takes place in subcortical regions of the brain. Thus, hunger and satiety signals are generated in regions of the brain, which are not associated with conscious experience. This points towards biological determinism of weight and challenges ideas of willpower and resultant moralization regarding body weight regulation. In this article, we will thus argue that in the context of dysregulation of hunger and

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Epigenetic Transgenerational Inheritance of Obesity Susceptibility

Cited by 105 publications

References 142 publications

Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic

Inter‐ and Transgenerational Effects of Paternal Exposure to Inorganic Arsenic

Madecassoside Inhibits Body Weight Gain via Modulating SIRT1-AMPK Signaling Pathway and Activating Genes Related to Thermogenesis

Obesity and responsibility: Is it time to rethink agency?

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