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Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes

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Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty

Bin Geng¹, Bo Cai, Feng Liao

¹Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Bei Jing, P.R. China.

|September 24, 2013

Summary

Inhibition of the cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system in fat cells boosts lipolysis, reducing obesity and insulin resistance. Conversely, H2S donors decrease lipolysis but also improve insulin sensitivity.

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Area of Science:

Biochemistry
Metabolic research
Endocrinology

Background:

Adipose tissue utilizes the endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system.
Hydrogen sulfide (H2S) precursors have been shown to inhibit catecholamine-stimulated lipolysis.
The CSE/H2S system's role in regulating lipolysis and its contribution to insulin resistance pathogenesis is hypothesized.

Purpose of the Study:

To investigate the role of the CSE/H2S system in regulating lipolysis.
To determine the impact of the CSE/H2S system on insulin resistance in obesity.

Main Methods:

Rat adipocytes were treated with a CSE inhibitor (DL-propargylglycine, PAG) or H2S precursors/donors (L-cysteine/pyridoxial phosphate or GYY4137).
Lipolysis was assessed by measuring glycerol levels.
The effects of PAG and GYY4137 on insulin resistance were evaluated in high-fat diet (HFD)-induced obese mice.

Main Results:

PAG increased basal and stimulated lipolysis, while L-cysteine and GYY4137 decreased it.
PAG elevated key lipolytic proteins (p-PKA substrate, perilipin 1, HSL), whereas L-cysteine and GYY4137 decreased them.
In HFD mice, PAG reduced fat mass and improved insulin sensitivity (glucose/insulin levels, HOMA, OGTT, ITT), while GYY4137 also ameliorated insulin resistance.

Conclusions:

Inhibition of the endogenous CSE/H2S system in adipocytes enhances lipolysis via the PKA-perilipin/HSL pathway, reducing fat mass and insulin resistance.
H2S donors decrease lipolysis but also mitigate HFD-induced insulin resistance.
The paradoxical regulation of lipolysis and insulin resistance by H2S suggests complex metabolic and endocrine roles in adipocytes.