Sex differences in the metabolic effects of diet-induced obesity vary by age of onset

Salinero, Abigail E.; Anderson, Brian; Zuloaga, Kristen L.

doi:10.1038/s41366-018-0023-3

Cited by 77 publications

(96 citation statements)

References 13 publications

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“…Energy expenditure and obesity are regulated by hypothalamus, in particular, the ARC that consists of POMC neurons. Studies have shown that POMC neurons modulate sex-specific changes of body weights in diet-induced obesity (Burke et al, 2016;Medrikova et al, 2012;Salinero et al, 2018). Here we show that POMC neuron-specific miR-7 knockdown and miR-17-92 knockout mice display sex-different response to high fat diet.…”

Section: Discussionsupporting

confidence: 57%

“…Interestingly, we have found that only female miR-7 knockdown mice and male miR-17-92 knockout mice display diet-induced obesity. Previous reports have shown sex-specific changes of body weights, which is regulated by POMC neurons (Burke et al, 2016;Medrikova et al, 2012;Salinero et al, 2018). However, how POMC neurons modulate sex-specific changes of body weight is unclear.…”

Section: Discussionmentioning

confidence: 96%

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MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

Sun

Gao

et al. 2018

Preprint

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Proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) in mammalian hypothalamus play important roles in regulating appetite, energy expenditure, and glucose and fat metabolisms. Diet-induced obesity often show sex-specific difference. But the underlying mechanisms remain unclear. Here we show that microRNA (miRNA) miR-7 and miR-17-92 are expressed in the mouse ARC, and mostly in POMC neurons. Knockdown of miR-7 and knockout of miR-17-92 specifically in POMC neurons aggravate diet-induced obesity only in females and males, respectively. Moreover, gene expression profile analysis identifies sex-differential genes in male and female ARCs in wildtype adult mice. Interestingly, these genes that normally show low-expression in the female and male ARCs display upregulated expression in female miR-7 knockdown and male miR-17-92 knockout mice, respectively. Our results demonstrate an important role of miRNAs in regulating sex-specific diet-induced obesity, likely through modulating expression of target genes that show sex-differential expression in the ARC of hypothalamus.

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Section: Discussionsupporting

confidence: 57%

Section: Discussionmentioning

confidence: 96%

MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

Sun

Gao

et al. 2018

Preprint

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“…Nevertheless, mouse and other in vivo preclinical models differ from humans in many known and unknown details, both intrinsic (eg, genetic, immune, 159-164 surface area: volume ratio, lifespan 165 ) and extrinsic (eg, captivity, diet, history), which, depending on the research question, may substantially affect translational relevance. [169][170][171][172] A wide variety of approaches are used to increase the predictive validity of mouse models. [169][170][171][172] A wide variety of approaches are used to increase the predictive validity of mouse models.…”

Section: Selection Of a Mouse Modelmentioning

confidence: 99%

Improving natural product research translation: From source to clinical trial

et al. 2019

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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“…Further, while 321 pre-menopausal women have considerable protection from numerous metabolic disease states 322 [39], the prevalence of overweight/obesity is higher in women in all age groups [40]. Chronic ad 323 libtum high-fat diet rodent studies of varying lengths have demonstrated that males and females 324 gain similar amounts of body weight, with females having greater body fat percentages [41,42]. 325…”

Section: Activity Components Of Energy Metabolism 252mentioning

confidence: 99%

“…can not determine the magnitude of activation of the different non-shivering thermogenic 409 tissues, which could potentially differ by baseline EE or sex. Third, the assessment of diet-410 induced weight gain in 9 -11 week old mice could be confounded by the previously observed 411 dependence of weight gain on age of diet initiation and sex [41]. Fourth, previous mouse work 412 has demonstrated that male mice defend different body core temperatures at different ambient 413 temperatures [27,65].…”

Section: Limitations 400mentioning

confidence: 99%

Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns

Morris

Noland

Allen

et al. 2019

Preprint

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Highlights Utilized ambient temperature differences as an experimental tool to study the impact of divergent baseline energy expenditure on metabolic adaptation to high-fat, high-sucrose diet. Baseline energy expenditure and sex interact to impact diet-induced changes in body composition and weight gain. The energy expenditure and sex interaction is a result of an inverse relationship between fat mass gain and weight-adjusted total energy expenditure, as well as, diet-induced non-shivering thermogenesis. These data support that the hypothesis that higher energy expenditure amplifies the coupling of energy intake to energy expenditure during energy dense feeding, resulting in reduced positive energy balance and reduced gains in weight and adiposity. First evidence that energy expenditure level plays a role in the composition of weight gained by female mice during acute HFHS feeding. This study further highlights issues with obesity/energy metabolism research performed in mice at sub-thermoneutral housing temperatures, particularly with sex comparisons. GRAPHIC ABSTRACTLegend: Male and female mice housed at 30⁰C had lower energy expenditure (EE) & energy intake (EI), while having greater energy balance (EB), during 7-day high-fat/high-sucrose (HFHS) feeding compared to male and female mice, respectively, housed at 20⁰C. However, female mice had lower EB compared to males at both housing temperature. Female mice housed at 30⁰C gained less weight than 30⁰C males but gained the same relative amount of fat mass during acute HFHS feeding. Interestingly, 20⁰C females gained the same amount of weight as 20⁰C males but gained primarily fat-free mass, while the males gained the same proportion of fat as 30⁰C males and females. ABSTRACT 1Objective: Long-term weight gain can result from cumulative small weight increases due to 2 short-term excess caloric intake during weekends and holidays. Increased physical activity may 3 mediate weight gain through increases in energy expenditure (EE) and reductions in energy 4 balance. Current methods for modulating mouse EE (e.g. -exercise, chemical uncouplers, etc.) 5 have confounding effects. However, it is known that mouse EE linearly increases as housing 6 temperature decreases below the thermoneutral zone. Methods: To determine how robust 7 differences in baseline EE impact 7-day changes in weight and body composition on low-fat and 8 high-fat, high-sucrose (HFHS) diets, we performed indirect calorimetry measurements in male 9 and female mice housed at divergent temperatures (20⁰C vs. 30⁰C). Results: As expected, 10 mice housed at 30⁰C have ~40% lower total EE and energy intake compared to 20⁰C mice 11 regardless of diet or sex. Energy balance was increased with HFHS in all groups, with ~30% 12 greater increases observed in 30⁰C versus 20⁰C mice. HFHS increased weight gain regardless 13 of temperature or sex. Interestingly, no HFHS-induced weight gain differences were observed 14 between females at different temperatures. In contrast, 30⁰C male mice on HFHS gained ~50% 15 more...

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Sex differences in the metabolic effects of diet-induced obesity vary by age of onset

Cited by 77 publications

References 13 publications

MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

MicroRNA miR-7 and miR-17-92 in POMC neurons are associated with sex-specific regulation of diet-induced obesity

Improving natural product research translation: From source to clinical trial

Divergent Energy Expenditure Impacts Mouse Metabolic Adaptation to Acute High-Fat/High-Sucrose Diet Producing Sexually Dimorphic Weight Gain Patterns

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