Acute Female Hypogonadism Alters Adipose Tissue Fatty Acid Storage Factors and Chylomicronemia
Open accessAbstract
CONTEXT: Chronic sex steroid deficiency has effects on adipose fatty acid (FA) storage mechanisms and fat oxidation, but the chronology of events are not well understood. OBJECTIVE: The objective of the study was to examine the acute effects of female sex steroid suppression on cellular mechanisms affecting abdominal and femoral subcutaneous adipose tissue FA storage. DESIGN: This study had a randomized, longitudinal, parallel study design. SETTING: The study was conducted at the Mayo Clinic Clinical Research Unit. PARTICIPANTS: Thirty-eight nonsmoking premenopausal women aged 18-50 years participated in the study. INTERVENTION: The intervention included randomization to receive one of the following: 1) no treatment (control), 2) 3.75 mg of Lupron, or 3) 3.75 mg of Lupron and estrogen, but not progesterone, replacement for 49 days, resulting in at least 4 weeks of sex steroid suppression. MAIN OUTCOME MEASURES: Body composition, fat cell size, postprandial chylomicron and nonchylomicron triglyceride concentrations, adipose tissue meal FA storage, direct free fatty acid storage, lipoprotein lipase, acyl CoA synthetase, and diacylglycerol acyltransferase activities, and CD36 content were measured. RESULTS: Compared with the control group, the fed state femoral lipoprotein lipase activity was reduced in women taking Lupron and those taking Lupron and estrogen replacement. In addition, we observed significantly greater postprandial chylomicronemia in the Lupron group than in the other two groups. There were no differences in overall fat storage and oxidation. Depending on the mode of data expression (per unit lipid vs per 1000 adipocytes), there were modest changes in acyl CoA synthetase, diacylglycerol acyltransferase, and CD36 in response to acute sex hormone suppression. CONCLUSIONS: Our results suggest estrogen and progesterone may have different effects on the regulation of FA metabolism and that acute sex steroid deficiency in women does not alter fat storage and oxidation.
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With chronic (at least 6 months) or acute (at least 4 weeks) testosterone suppression, the proportion of meal fat stored in lower body subcutaneous adipose tissue is greater than in males with normal testosterone concentrations.
“However, with both chronic (at least 6 months) (20) and acute (at least 4 weeks) (115) testosterone suppression, the proportion of meal fat stored in lower body subcutaneous adipose tissue is greater than in those with normal testosterone concentrations.”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The citation (115) is attached to the acute-suppression part of the sentence. The Discussion (page unavailable) explicitly reports no effect of acute sex-hormone suppression on regional meal fatty-acid storage. The study examined estrogen and progesterone suppression in premenopausal women, not testosterone suppression in males. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredNeither 7 days nor 4 weeks of gonadal hormone suppression in young men using GnRH agonists changes postprandial fat oxidation or meal fat oxidation following a mixed meal.
“However, neither 7 days (117) nor 4 weeks (115) of gonadal hormone suppression in young men using GnRH agonists changes postprandial fat oxidation (indirect calorimetry) or meal fat oxidation (isotopic tracers) following consumption of a mixed meal.”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The 'Substrate and meal FA oxidation' section reports no differences in postprandial total fatty acid oxidation or meal fatty acid oxidation after at least four weeks of suppression. But the study enrolled premenopausal women, not young men. The seven-day result is attached to a different citation in the citing sentence and is not assessed here; page numbers are not available in the supplied passages. (LLM, conf=0.89)
Experimental — accuracy not yet measuredThe proportion of meal fat stored in upper body subcutaneous adipose tissue is greater than in lower body subcutaneous adipose tissue regardless of whether males have normal, chronically low, or acutely reduced testosterone status.
“The proportion of meal fat stored in upper body subcutaneous adipose tissue is greater than in lower body subcutaneous adipose tissue regardless of whether males have normal (20, 115), chronically low (20), or acutely reduced (115) testosterone status.”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The Regional meal and direct FA storage section reports a greater proportion of meal fat stored in upper- than lower-body subcutaneous tissue in two treatment groups of women; the control group showed only a trend. This supports the regional comparison, but the study does not establish it in men with normal, chronically low, or acutely reduced testosterone. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe increase in meal fat storage in acutely hypogonadal males was associated with greater LPL and ACS activity in the femoral region.
“This increase in meal fat storage was associated with greater LPL and ACS activity in the femoral region of acutely hypogonadal males, indicating a role of these two enzymes in the storage of meal FA in the femoral subcutaneous adipose tissue depot (115).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The LPL activity and meal FA storage section reports an association between femoral LPL activity and meal-fat storage when all groups of women were combined, but not a significant femoral association within the acutely hypogonadal group. The Discussion says acute hormone suppression did not increase regional meal-fat storage; its femoral ACS association concerns direct FFA storage, not meal-fat storage. The study examined women, not males. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLPL and ACS activity may play a role in storage of meal FA in the femoral subcutaneous adipose tissue depot.
“This increase in meal fat storage was associated with greater LPL and ACS activity in the femoral region of acutely hypogonadal males, indicating a role of these two enzymes in the storage of meal FA in the femoral subcutaneous adipose tissue depot (115).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The “LPL activity and meal FA storage” section reports a correlation between fed LPL activity and femoral meal-fatty-acid storage across the combined groups, supporting a possible role for LPL. But this study examined women, not acutely hypogonadal males; its ACS association concerned direct FFA storage rather than meal-fatty-acid storage. The Discussion also reports no effect of acute hormone suppression on regional meal-fatty-acid storage, contrary to the cited sentence’s claimed increase. (LLM, conf=0.88)
Experimental — accuracy not yet measured
LPL activity about 6 hours after breakfast correlates well with the amount of meal fat stored in abdominal and femoral adipose tissue.
“In response to meal ingestion, there are variable increases in adipose tissue LPL activity (145), and the activity that is observed ~ 6 hours after breakfast consumption is well correlated with the amount of meal fat stored in abdominal and femoral adipose tissue (20–22, 114, 115).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
Postprandial chylomicron triacylglycerol concentrations are not different between eugonadal men and those with acute or chronic testosterone deprivation.
“In contrast, postprandial chylomicron triacylglycerol concentrations are not different between eugonadal men and those with acute or chronic testosterone deprivation (20, 115).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The Abstract describes a study of premenopausal women, and the Discussion reports higher chylomicron triglyceride concentrations in women receiving Lupron than in controls. Searches for eugonadal men, testosterone deprivation, and male hypogonadism found no passage comparing postprandial chylomicron concentrations in men with acute or chronic testosterone deprivation. The finding in women does not establish or contradict the claim about men. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn men who received GnRH agonists to suppress gonadal function for at least 4 weeks, meal fat storage in the femoral depot was almost double that of control males and those receiving GnRH agonists plus transdermal testosterone replacement.
“With regards to the efficiency of meal fat storage, acute suppression of male sex steroids, men who received GnRH agonists to suppress gonadal function for at least 4 weeks stored almost double the amount of meal fat (mg meal fat/g adipose lipid relative to meal size) in the femoral depot than control males and those receiving GnRH agonists plus transdermal testosterone replacement (115).”
From Sex differences in the metabolism of glucose and fatty acids by adipose tissue and skeletal muscle in humans (2025) · cites this paper as [115]
The Subjects and Study design sections describe women given Lupron, with or without transdermal estrogen—not men given transdermal testosterone. The Discussion reports no effect of acute suppression on regional meal-fat storage in those women. Our copy does not address the claimed near-doubling of femoral meal-fat storage in men. (LLM, conf=0.78)
Experimental — accuracy not yet measured
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- Authors
- Santosa, S., Bonnes, S. L., & Jensen, M. D.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Jensen, Michael D.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-05
- Volume
- 101
- Issue
- 5
- Pages
- 2089-2098
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4870847
- OpenAlex
- W2310309351
- Cited by
- 16
- References
- 35
- Citations by year
- 2026: 2 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- AbbVie
- National Institutes of Health (DK-50456, RR024150, DK-40484)
- Natural Sciences and Engineering Research Council of Canada
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK050456, R37DK040484, U24DK100469, R01DK045343, R01DK040484)
- National Center for Research Resources (RR-024150, DK50456, UL1RR024150)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- female hypogonadism, estrogen deficiency, progesterone, chylomicronemia, lipoprotein lipase, acyl-CoA synthetase, diacylglycerol acyltransferase, CD36, free fatty acid uptake, triglyceride metabolism, fat oxidation, body composition, premenopausal women, leuprolide
- MeSH terms
- Adipose Tissue, Adolescent, Adult, Body Composition, Chylomicrons, Coenzyme A Ligases, Estrogens, Fatty Acids, Nonesterified, Female, Fertility Agents, Female, Humans, Hypogonadism, Lipoprotein Lipase, Longitudinal Studies, Middle Aged, Leuprolide, CD36 Antigens, Postprandial Period, Diacylglycerol O-Acyltransferase, Young Adult
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