What are the metabolic fates of lipids released from adipocytes after photobiomodulation—oxidation, re‑esterification, or redistribution?
Executive summary
Photobiomodulation (PBM) applied to adipose tissue consistently reduces the generation and release of free fatty acids (FFA) from adipocytes in multiple preclinical models, shifting the immediate metabolic fate away from elevated plasma oxidation and toward intracellular retention and lowered systemic redistribution, with AMPK signalling implicated as a key mediator [1] [2] [3]. Evidence that PBM directly increases mitochondrial fatty acid oxidation is indirect and limited to changes in mitochondrial function and reduced lipid peroxidation; most data point to decreased lipolysis and altered lipogenesis rather than a straightforward increase in whole‑body fatty acid oxidation [4] [5] [6].
1. PBM reduces lipolysis and lowers FFA release from adipocytes
Multiple controlled animal and cell studies report that PBM decreases triglyceride hydrolysis and extracellular free fatty acid release from white adipocytes in a dose‑ and time‑dependent manner, producing falls in measured extracellular FFA and glycerol consistent with suppressed lipolysis [1] [7] [2]. These reductions translate in preclinical models to lower circulating FFA and improved markers of insulin sensitivity, implying that the first major effect of PBM on lipid fate is to prevent or blunt flux of fatty acids out of adipocytes [1] [2].
2. Re‑esterification and intracellular retention appear to be a dominant fate
Because PBM lowers extracellular FFA while studies concurrently report decreased lipogenesis markers in liver and altered adipocyte lipid handling, the balance of evidence supports increased intracellular retention or re‑esterification of liberated fatty acids back into triglyceride stores rather than terminal release into plasma; several reports frame PBM’s net effect as reducing lipolytic output and permitting adipocytes and liver to re‑route lipids away from harmful circulation [1] [7] [3].
3. Oxidation: evidence is indirect and not definitive for increased whole‑body FAO
PBM modulates mitochondrial membrane potential, ATP and reactive oxygen species in adipose‑derived cells—effects that could alter cellular oxidation capacity—but direct quantitative evidence that PBM increases fatty acid β‑oxidation in vivo is limited in the available literature [4] [5]. Parallel findings of reduced lipid peroxidation and oxidative stress after PBM indicate lowered damaging oxidation products rather than a clear upregulation of oxidative disposal of fatty acids, so claiming PBM drives systemic FA oxidation would overstate what the data currently show [6] [5].
4. Redistribution to other tissues (liver, BAT) is altered but complex
PBM studies show improvements in hepatic lipid metabolism and reductions in hepatic lipogenesis via AMPK signalling, implying that PBM does not simply shuttle more fatty acids to the liver for storage or oxidation; instead it appears to reduce the liver’s lipogenic response and overall dyslipidemia in diet‑induced models [3] [8]. Broader lipidomics and metabolic‑flux literature emphasizes that redistribution depends heavily on physiological context and lipolytic flux—when lipolysis is suppressed, downstream production of lipid mediators and redistribution to tissues is substantially modified, consistent with PBM reducing harmful redistribution [9] [10].
5. Mechanistic signals: AMPK/CaMKKβ and enzyme modulation point to re‑routing not wholesale oxidation
Mechanistic studies link PBM to rises in intracellular calcium, activation of CaMKKβ→AMPK signalling and downstream suppression of lipogenesis, along with proposed modulation of hormone‑sensitive lipase and lipoprotein lipase activity; these pathways collectively favor lowering FFA release and shifting metabolic programs toward controlled lipid handling rather than a large increase in β‑oxidation [3] [7] [8].
6. Caveats, gaps and the balanced conclusion
All strong experimental evidence comes from cell cultures and animal models with variable PBM wavelengths, doses and endpoints; human clinical data remain sparse and some observational reports assert benefits on lipid profiles without mechanistic confirmation [2] [7]. In sum, available reporting supports that after PBM the predominant metabolic fates of lipids released (or poised for release) from adipocytes are reduced extracellular release and increased intracellular re‑esterification/retention with altered redistribution and suppressed hepatic lipogenesis, while direct enhancement of systemic fatty‑acid oxidation is plausible but not yet convincingly demonstrated by the cited studies [1] [3] [4] [5] [6].