Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

Vieira Potter, Victoria J.; Strissel, Katherine J.; Xie, Chen; Chang, Eugene; Bennett, Grace; Defuria, Jason; Obin, Martin S.; Greenberg, Andrew S.

doi:10.1210/en.2011-2006

Cited by 99Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismCardiovascular Disease and Adiposity

Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

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Vieira Potter, Victoria J., Strissel, Katherine J., Xie, Chen, Chang, Eugene, Bennett, Grace, Defuria, Jason, Obin, Martin S., Greenberg, Andrew S.·2012·Endocrinology

DOI 10.1210/en.2011-2006PMC PMC3423617

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Abstract

Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (∼31 g) became fatter than SHM mice (∼26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MΦ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (−20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-γ (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity.

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The decline in gonadal sex hormone production that occurs in post-menopausal women and in aged men coincides with increased sex hormone synthesis within adipose tissue.
“The decline in gonadal sex hormone production that occurs in post-menopausal women and in aged men coincides with increased sex hormone synthesis within adipose tissue (76, 98).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [76]
The Discussion (page not provided) discusses loss of ovarian hormones after menopause, supporting the claim about declining gonadal hormone production in women. It does not address hormone decline in aged men or say that sex hormone synthesis increases within adipose tissue. (LLM, conf=0.82)
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Female mice and rats that have undergone ovariectomy have increased adiposity and are more prone to diet-induced obesity than sham-operated mice, with elevated adipose tissue inflammation.
“Female mice and rats that have undergone ovariectomy (OVX), effectively removing all gonadal estrogens, have increased adiposity and are more prone to diet-induced obesity than sham-operated mice, with elevated adipose tissue inflammation (75–79).”
From Metabolic impact of endogenously produced estrogens by adipose tissue in females and males across the lifespan (2025) · cites this paper as [76]
The Results section (‘After early rapid weight gain…’; page unavailable) reports greater fat mass in ovariectomized mice during the first 12 weeks, but no adiposity difference from sham-operated mice by 17 weeks. The Discussion (page unavailable) reports greater adipose-tissue inflammation in ovariectomized mice. This study used chow-fed mice, not rats, and does not establish greater susceptibility to diet-induced obesity. (LLM, conf=0.89)
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Authors: Vieira Potter, V. J., Strissel, K. J., Xie, C., Chang, E., Bennett, G., Defuria, J., Obin, M. S., & Greenberg, A. S.
Affiliations: Obesity and Metabolism Laboratory, U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111
Tufts University (US)
Corresponding author: Greenberg, Andrew S.
ORCID: Xie, Chen
Bennett, Grace
Greenberg, Andrew S.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2012-09-01
Volume: 153
Issue: 9
Pages: 4266-4277
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2011-2006
PMC: PMC3423617
OpenAlex: W2055185510
Cited by: 99
References: 41
Citations by year: 2026: 5 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 2 · 2019: 10 · 2018: 9 · 2017: 10 · 2016: 7 · 2015: 13 · 2014: 7 · 2013: 7
FWCI: 6.47
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: public-domain
Locations: Endocrinology (publishedVersion, public-domain)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Agriculture (58-1950-7-707)
National Institutes of Health
National Heart, Lung, and Blood Institute (GB-T32-HL069772-09, T32HL069772)
National Institute of Diabetes and Digestive and Kidney Diseases (T32DK062032, R24 DK0867669, DK082574, R24DK087669, T32- DK062032-20, R01DK082574, R01DK074979)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: ovariectomy, menopause, adipose tissue inflammation, insulin resistance, estrogen deficiency, perigonadal adipose tissue, macrophages, T cells, arginase-1, cytotoxic T lymphocyte antigen 4, Th1/Th2 polarization, interferon-gamma, IL-12, obesity, weight gain, C57BL/6 mice
MeSH terms: Adipose Tissue, Animals, Body Composition, Body Weight, Female, Flow Cytometry, Immunohistochemistry, Insulin Resistance, Ovariectomy, Polymerase Chain Reaction, Adiposity, Mice

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Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity

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