Surreal illustration of hormonal and metabolic pathways with RAMP3 protein, symbolizing postmenopausal weight management.

Unlocking the Secrets of Postmenopausal Weight Gain: How RAMP3 Holds the Key

Lena Voss in Health & Wellness December 2025 • 4 min read.

"New research reveals the crucial role of RAMP3 deficiency in enhancing postmenopausal obesity and metabolic disorders, offering potential therapeutic targets."

Weight gain after menopause is a common struggle for many women, often accompanied by increased visceral fat and insulin resistance. This isn't just about the numbers on the scale; it's a shift in how your body manages energy, influenced by hormonal changes and metabolic processes. Understanding these underlying factors is key to addressing postmenopausal weight gain effectively.

Adrenomedullin (AM), a peptide known for its role in vasodilation, has broader physiological effects. RAMP3, a receptor activity-modifying protein, interacts with the AM receptor and is believed to be activated by estrogen. Recent studies suggest that RAMP3 plays a significant role in the metabolic changes that occur postmenopause, making it a critical area of research for understanding and combating related weight issues.

A groundbreaking study has investigated how RAMP3 deficiency enhances postmenopausal obesity and metabolic disorders. By exploring the effects of ovariectomy (OVX) and a high-fat diet in RAMP3 knockout mice, researchers have uncovered potential therapeutic targets to combat weight gain and metabolic imbalances during and after menopause. This article will breakdown those findings.

How Does RAMP3 Deficiency Impact Postmenopausal Obesity?

Surreal illustration of hormonal and metabolic pathways with RAMP3 protein, symbolizing postmenopausal weight management.

The study compared RAMP3 knockout mice (RAMP3-/-) with wild-type mice, both undergoing ovariectomy (OVX) to simulate postmenopausal conditions and fed a high-fat diet for 10 weeks. The results indicated that RAMP3-/- OVX mice experienced significantly greater obesity and adipose tissue weight gain compared to their wild-type counterparts. This suggests that RAMP3 plays a protective role against excessive weight gain following estrogen reduction.

Further analysis revealed that RAMP3-/- OVX mice had higher serum insulin levels, indicating potential insulin resistance. This is crucial because insulin resistance can lead to increased fat storage and metabolic dysfunction, exacerbating weight gain. Understanding this mechanism can pave the way for targeted interventions to improve insulin sensitivity.

Increased Body Weight: RAMP3 deficient mice showed greater weight gains, especially in visceral fat.
Insulin Resistance: These mice exhibited higher insulin levels, indicating reduced insulin sensitivity.
Inflammation: White adipose tissue showed increased inflammation, further disrupting metabolic balance.
Hepatic Steatosis: The condition exacerbated fatty liver, highlighting RAMP3's role in liver health.

In periuterine white adipose tissue (WAT) from RAMP3-/- OVX mice, researchers found lower expression of lipolysis-related factors and higher expression of inflammation-related factors. Lipolysis is the breakdown of fats, and its reduction means the body is less efficient at burning fat. Meanwhile, increased inflammation in adipose tissue is linked to metabolic disorders and insulin resistance. This dual impact significantly contributes to weight gain and metabolic dysfunction in postmenopausal conditions.

The Future of RAMP3 in Weight Management

This research underscores the potential of RAMP3 as a therapeutic target for managing postmenopausal obesity and related metabolic disorders. By understanding the specific mechanisms through which RAMP3 influences weight gain, insulin sensitivity, and inflammation, scientists can develop targeted treatments to help women maintain a healthy weight and metabolic profile during and after menopause. Further studies are needed to explore how these findings can be translated into effective therapies, offering new hope for those struggling with postmenopausal weight management.

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This article is based on research published under:

DOI-LINK: 10.1016/j.peptides.2018.10.006, Alternate LINK

Title: Ramp3 Deficiency Enhances Postmenopausal Obesity And Metabolic Disorders

Subject: Cellular and Molecular Neuroscience

Journal: Peptides

Publisher: Elsevier BV

Authors: Teng Liu, Akiko Kamiyoshi, Megumu Tanaka, Shiho Iida, Takayuki Sakurai, Yuka Ichikawa-Shindo, Hisaka Kawate, Kazutaka Hirabayashi, Kun Dai, Nanqi Cui, Masaaki Tanaka, Yangxuan Wei, Keisei Nakamura, Shuhei Matsui, Akihiro Yamauchi, Takayuki Shindo

Published: 2018-12-01

Everything You Need To Know

What is RAMP3 and why is it important in the context of postmenopausal weight gain?

RAMP3, or Receptor Activity-Modifying Protein 3, interacts with the Adrenomedullin (AM) receptor and is influenced by estrogen. It plays a significant role in metabolic changes that occur after menopause. A deficiency in RAMP3 can lead to increased weight gain, insulin resistance, and inflammation, particularly in visceral fat. This is important because it highlights RAMP3 as a potential therapeutic target for managing weight and metabolic health postmenopause. The implications of these findings are that by understanding RAMP3's role, targeted treatments can be developed to help women maintain a healthy weight and metabolic profile during and after menopause. Further studies are needed to determine how these findings can lead to effective therapies.

What is ovariectomy (OVX) and why is it used in research related to menopause?

Ovariectomy (OVX) is a surgical procedure that removes the ovaries, simulating the hormonal changes that occur during menopause in animal models. It's significant in research because it allows scientists to study the effects of estrogen loss on various physiological processes, such as weight gain and metabolic function. The implications of using OVX in studies are that it provides a controlled way to investigate postmenopausal conditions and identify potential therapeutic targets for managing related health issues.

What is insulin resistance and why is it a concern in postmenopausal women?

Insulin resistance is a condition where the body's cells become less responsive to insulin, a hormone that regulates blood sugar levels. This can lead to higher serum insulin levels, increased fat storage, and metabolic dysfunction, exacerbating weight gain. It's important because it's a key factor in postmenopausal weight gain and related metabolic disorders. If unaddressed it can increase the risk of type 2 diabetes and cardiovascular diseases. The connection to RAMP3, a deficiency can increase Insulin resistance.

What is white adipose tissue (WAT) and how does it relate to weight gain after menopause?

White adipose tissue (WAT) is a type of fat tissue that stores energy. In the context of postmenopausal weight gain, changes in WAT, such as increased inflammation and reduced lipolysis (the breakdown of fats), contribute to metabolic dysfunction and weight gain. This is important because understanding these changes can help in developing targeted interventions to improve metabolic health. The decreased expression of lipolysis-related factors and increased expression of inflammation-related factors in WAT from RAMP3 deficient mice contributes to weight gain and metabolic dysfunction.

What is Adrenomedullin (AM) and what is its role?

Adrenomedullin (AM) is a peptide known for its role in vasodilation but has broader physiological effects. It interacts with RAMP3, and this interaction influences metabolic processes. This is significant because it links hormonal regulation with metabolic health. Further research into the relationship between Adrenomedullin and RAMP3 may open new avenues for therapeutic interventions targeting postmenopausal weight gain and metabolic disorders.