International journal of molecular sciencesJul 28, 2026

HMB helps prevent muscle cell shrinking and restores daily rhythm in muscle cells

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

HMB treatment significantly improved cell viability, surface area, and fiber diameter in C2C12 myotubes exposed to dexamethasone-induced muscle atrophy.

HMB reduced the expression of CBL-B, MuRF1, and Atrogin1, which are associated with muscle breakdown.
Increased myogenin expression was observed with HMB treatment compared to conditions of muscle atrophy.
HMB treatment did not activate AKT or mTOR, but increased phosphorylation of P70S6K and S6 through a phospholipase D-dependent mechanism.
HMB restored circadian clock gene expression disrupted by dexamethasone and normalized expression patterns.
The treatment enhanced circadian rhythmic amplitude and advanced phase timing, indicating improved robustness of the circadian clock.

Simplified

β-hydroxy-β-methylbutyrate (HMB), a bioactive metabolite of leucine, is widely recognized for its anabolic and anti-catabolic effects in skeletal muscle. However, the molecular mechanisms underlying these effects, particularly in relation to circadian regulation, remain incompletely understood. Here, we investigated the impact of HMB on dexamethasone-induced muscle atrophy in C2C12 myotubes, with a focus on anabolic signaling and circadian clock regulation. C2C12 myotubes were treated with HMB or HMB after dexamethasone-induced atrophy. HMB treatment significantly improved cell viability, surface area and fiber diameter by reducing expression of CBL-B, MuRF1 and Atrogin1, key mediators of muscle proteolysis, and increasing myogenin expression compared with atrophic conditions. While HMB did not activate AKT or mTOR, it robustly increased phosphorylation of P70S6K and S6 through a phospholipase D (PLD)-dependent mechanism. HMB restored disrupted circadian clock gene expression induced by dexamethasone, including normalization of expression patterns. HMB also enhanced circadian rhythmic amplitude and advanced phase timing, indicating improved clock robustness. These findings identify circadian regulation as a novel target of HMB action and demonstrate that HMB preserves muscle homeostasis through coordinated modulation of anabolic signaling and intrinsic circadian machinery. This study provides mechanistic insight into how HMB protects against muscle atrophy and highlights circadian regulation as an important contributor to skeletal muscle health.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

0%of authors

0 of 4

authors report competing interests

4 report none

PubMed

HMB helps prevent muscle cell shrinking and restores daily rhythm in muscle cells

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief