Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage

Simpson, Stephen J.; Raubenheimer, David; Black, Kirsten; Conigrave, Arthur D.

doi:10.1111/1471-0528.17290

Cited by 8 publications

(5 citation statements)

References 61 publications

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“…As expected, the OVX mice presented increased FSH in serum and body weight gain (Supplementary Fig. S1A and B), which are the laboratory and clinical features in estrogen-deficiency conditions 19 . Due to the lack of ovarian estradiol production and its inhibitory feedback, FSH levels may rise in an attempt to stimulate the ovaries 20 .…”

Section: Discussionsupporting

confidence: 78%

Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model

Baek,

Kang,

Lee

et al. 2024

Sci Rep

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The high risk of neurological disorders in postmenopausal women is an emerging medical issue. Based on the hypothesis of altered estrogen receptors (ERα and β) after the decline of estrogen production, we investigated the changes in ERs expressions across brain regions and depressive/amnesic behaviors. C57BL/6J female mice were ovariectomized (OVX) to establish a menopausal condition. Along with behavior tests (anxiety, depression, and memory), the expression of ERs, microglial activity, and neuronal activity was measured in six brain regions (hippocampus, prefrontal cortex, striatum, raphe nucleus, amygdala, and hypothalamus) from 4 to 12 weeks after OVX. Mice exhibited anxiety- and depressive-like behaviors, as well as memory impairment. These behavioral alterations have been linked to a suppression in the expression of ERβ. The decreased ERβ expression coincided with microglial-derived neuroinflammation, as indicated by notable activations of Ionized calcium-binding adapter molecule 1 and Interleukin-1beta. Additionally, the activity of brain-derived neurotrophic factor (BDNF), particularly in the hippocampus, decreased in a time-dependent manner from 4 to 12 weeks post-OVX. Our study provides evidence shedding light on the susceptibility to memory impairment and depression in women after menopause. This susceptibility is associated with the suppression of ERβ and alteration of ERα in six brain regions.

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Section: Discussionsupporting

confidence: 78%

Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model

Baek,

Kang,

Lee

et al. 2024

Sci Rep

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“…This work suggests an integrative model of obesity, at the centre of which is the acute sensitivity to protein deficiency or amino acid imbalance that humans accompanied by reduced energy requirements (9%) owing to a reduction in physical activity. Simultaneously meeting the higher-protein target while remaining in energy balance requires shifting to a higher per cent protein diet (red radial), whereas reaching the protein intake target while remaining on a 16% protein diet requires ingesting excess calories (purple arrow) (from [101]).…”

Section: Discussionmentioning

confidence: 99%

“…This is because, as the protein target increases linearly, the number of extra calories that must be eaten to attain the higher target on a given low-protein diet will increase exponentially. For example, a disproportionate increase in protein to nPE requirements may explain body weight gain, increased fat mass and decreased lean body mass with age in both sexes [ 15 ] and across the menopause transition in women [ 101 ] ( figure 6 ). Ageing and menopause are associated with reduced skeletal muscle mass and net bone resorption, increased protein catabolism, impaired protein synthesis and elevated FGF21.…”

Section: Moving Targets: Using Protein Leverage To Generate New Hypot...mentioning

confidence: 99%

Protein appetite as an integrator in the obesity system: the protein leverage hypothesis

Raubenheimer,

Simpson

2023

Phil. Trans. R. Soc. B

Self Cite

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Despite the large volume and extensive range of obesity research, there is substantial disagreement on the causes and effective preventative strategies. We suggest the field will benefit from greater emphasis on integrative approaches that examine how various potential contributors interact, rather than regarding them as competing explanations. We demonstrate the application of nutritional geometry, a multi-nutrient integrative framework developed in the ecological sciences, to obesity research. Such studies have shown that humans, like many other species, regulate protein intake more strongly than other dietary components, and consequently if dietary protein is diluted there is a compensatory increase in food intake—a process called protein leverage. The protein leverage hypothesis (PLH) proposes that the dilution of protein in modern food supplies by fat and carbohydrate-rich highly processed foods has resulted in increased energy intake through protein leverage. We present evidence for the PLH from a variety of sources (mechanistic, experimental and observational), and show that this mechanism is compatible with many other findings and theories in obesity research. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part II)’.

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“…Nutrition recommendations tailored to the individual should account for changing hormones, health history, food preferences, and nutrition accessibility, among other factors. The combination of a decrease in estrogen and increase in FSH during the menopause transition promotes the breakdown of lean tissue and in turn increases protein needs [20]. With the decrease in insulin sensitivity with estrogen's decline, carbohydrate metabolism changes during the menopause transition.…”

Section: Nutritionmentioning

confidence: 99%

Menopause, weight, and metabolic health – considerations for a patient centered, multidisciplinary approach

Lowy¹,

Kasianchuk

2023

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of reviewTo examine the complexity of weight and metabolic changes during the menopausal transition and propose a multidisciplinary care approach to support long-term metabolic health. Recent findingsMenopause, weight and metabolic health changes are influenced by many interplaying factors, and therefore, require a multipronged, multidisciplinary patient centered approach. This approach should start with a medical history and examination. Additional key components include: behavior change principles, mental health evaluation, gynecological care, nutrition, exercise recommendations and sleep care. In addition, when appropriate, weight loss pharmacotherapy and surgical options should be considered. Metabolic health is a long-term chronic process and improvement requires a chronic management approach.

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Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage

Cited by 8 publications

References 61 publications

Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model

Linking alterations in estrogen receptor expression to memory deficits and depressive behavior in an ovariectomy mouse model

Protein appetite as an integrator in the obesity system: the protein leverage hypothesis

Menopause, weight, and metabolic health – considerations for a patient centered, multidisciplinary approach

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