Pathophysiological mechanisms linking sarcopenic obesity to mental health among older people: A state-of-the-art review linking peripheral signals to neural consequences

Wilson Kin Chung Leung; Sonata Suk Yu Yau; Connie Yim Ching Yau; Simon Ching Lam; Lorna Kwai Ping Suen; Wilson Kin Chung Leung; Sonata Suk Yu Yau; Connie Yim Ching Yau; Simon Ching Lam; Lorna Kwai Ping Suen

doi:10.3934/publichealth.20260054

AIMS Public Health

2026, Volume 13, Issue 4: 1034-1068. doi: 10.3934/publichealth.20260054

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Review

Pathophysiological mechanisms linking sarcopenic obesity to mental health among older people: A state-of-the-art review linking peripheral signals to neural consequences

1.
School of Nursing, Tung Wah College, 16/F, Ma Kam Chan Memorial Building, 31 Wylie Road, Kowloon, Hong Kong SAR, People's Republic of China
2.
Translational Research Centre for Digital Mental Health, Tung Wah College, Kowloon, Hong Kong SAR, People's Republic of China
3.
Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, People's Republic of China

Received: 29 April 2026 Revised: 25 June 2026 Accepted: 27 July 2026 Published: 20 October 2026

Background
Sarcopenia and obesity are global health concerns that usually precede the onset and development of adverse health outcomes among older people. Recent findings have shown that sarcopenic obesity is a significant risk factor for geriatric mental health conditions, especially depression. However, it remains mechanistically unclear how sarcopenic obesity-specific interactions among adipose tissues, skeletal muscles, and/or the sites of intramuscular lipid accumulation adversely affect the mental health of older adults.
Scope
Peer-reviewed articles on both clinical (humans) and preclinical (experimental animals and cultured cells) studies primarily aiming at elucidating the associations between sarcopenic obesity and mental health and the molecular mechanisms behind, with English full-text available, were included.
Key findings
In this review, we reviewed the definitions, diagnostic criteria [European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO)], screening and staging, and health consequences of sarcopenic obesity. We discuss potential mechanisms underlying the association between sarcopenic obesity and mental health, including dysfunction of the hypothalamic–pituitary–adrenal axis, chronic systemic low-grade inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor alpha), oxidative stress, and an imbalance between adipokines (leptin, fatty acid–binding proteins, adiponectin, and resistin) and myokines (brain-derived neurotrophic factor, irisin, fibroblast growth factor 21, and apelin). Additionally, we gain novel insights into the deficiency in store-operated Ca²⁺ entry regulatory factor in immune cells, triggering the release of proinflammatory cytokines and the influx of peripheral tissue factors into the brain via disrupting the blood–brain barrier.
Conclusions
A deep understanding of the molecular pathways behind the onset of sarcopenic obesity-related mental disorders can provide a future perspective for the identification of evidence-based biomarkers and therapeutic targets in human clinical studies.
- sarcopenic obesity,
- sarcopenia,
- muscle loss,
- overweight,
- obesity,
- mental health,
- mental disorders,
- mental well-being,
- exercise training,
- resistance training
Citation: Wilson Kin Chung Leung, Sonata Suk Yu Yau, Connie Yim Ching Yau, Simon Ching Lam, Lorna Kwai Ping Suen. Pathophysiological mechanisms linking sarcopenic obesity to mental health among older people: A state-of-the-art review linking peripheral signals to neural consequences[J]. AIMS Public Health, 2026, 13(4): 1034-1068. doi: 10.3934/publichealth.20260054

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Abstract

Background

Sarcopenia and obesity are global health concerns that usually precede the onset and development of adverse health outcomes among older people. Recent findings have shown that sarcopenic obesity is a significant risk factor for geriatric mental health conditions, especially depression. However, it remains mechanistically unclear how sarcopenic obesity-specific interactions among adipose tissues, skeletal muscles, and/or the sites of intramuscular lipid accumulation adversely affect the mental health of older adults.

Scope

Peer-reviewed articles on both clinical (humans) and preclinical (experimental animals and cultured cells) studies primarily aiming at elucidating the associations between sarcopenic obesity and mental health and the molecular mechanisms behind, with English full-text available, were included.

Key findings

In this review, we reviewed the definitions, diagnostic criteria [European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO)], screening and staging, and health consequences of sarcopenic obesity. We discuss potential mechanisms underlying the association between sarcopenic obesity and mental health, including dysfunction of the hypothalamic–pituitary–adrenal axis, chronic systemic low-grade inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor alpha), oxidative stress, and an imbalance between adipokines (leptin, fatty acid–binding proteins, adiponectin, and resistin) and myokines (brain-derived neurotrophic factor, irisin, fibroblast growth factor 21, and apelin). Additionally, we gain novel insights into the deficiency in store-operated Ca²⁺ entry regulatory factor in immune cells, triggering the release of proinflammatory cytokines and the influx of peripheral tissue factors into the brain via disrupting the blood–brain barrier.

Conclusions

A deep understanding of the molecular pathways behind the onset of sarcopenic obesity-related mental disorders can provide a future perspective for the identification of evidence-based biomarkers and therapeutic targets in human clinical studies.

Abbreviations

ASM

appendicular skeletal muscle

ASMI

appendicular skeletal muscle index

AWGS

Asian Working Group on Sarcopenia

BBB

blood–brain barrier

BDNF

brain-derived neurotrophic factor

BIA

bioelectrical impedance analysis

BMI

body mass index

body weight

Ca²⁺

calcium ions

Cav1

L-type channels

CNS

central nervous system

CRP

C-reactive protein

DXA

dual-energy X-ray absorptiometry

EASO

European Association for the Study of Obesity

ERK1/2

Mitogen-activated protein kinase

ESPEN

European Society for Clinical Nutrition and Metabolism

EWGSOP

European Working Group on Sarcopenia in Older People

FABP

fatty acid–binding proteins

FFAs

free fatty acids

FGF21

fibroblast growth factor 21

FNIH

Foundation of the National Institutes of Health

handgrip

HPA

hypothalamic-pituitary-adrenal

IGF-1

insulin-like growth factor 1

IL-4

interleukin-4

IL-6

interleukin-6

IL-18

interleukin-18

insulin resistance

IWGS

International Working Group on Sarcopenia

MDD

major depressive disorder

miRNAs

microRNAs

MMP

matrix metalloproteinases

ROS

reactive oxygen species

SARAF

stored-operated calcium entry regulatory factor

sarcopenic obesity

STAT3

signal transducer and activator of transcription 3

T2D

type 2 diabetes

TNF-α

tumor necrosis factor alpha

TrkB

tyrosine kinase 2

TRP

transient receptor potential

waist circumference

Funding

This work was supported by School Research Grant (grant number SRFP250002) of Tung Wah College and College Research Grant (grant number CRG2023/01) of Tung Wah College, Hong Kong SAR, People's Republic of China.
The funding source had no involvement in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Authors' contributions

Leung WKC, Yau SSY, Lam SC, and Suen LKP conceived and designed the study. Leung WKC and Yau SSY designed search strategies. Leung WKC and Yau CYC conducted literature search and data extraction. Leung WKC prepared figures 1–5, tables 1–5, and appendices 1–3. Leung WKC, Yau SSY, Yau CYC, Lam SC, and Suen LKP reviewed, commented on, and edited the main content. All authors read and approved of the final manuscript.

Conflict of interest

Lorna Kwai Ping Suen is an editorial board member for AIMS Public Health and was not involved in the editorial review or the decision to publish this article. The authors declare no financial or non-financial competing interests.

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