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Review
. 2023 May 29;12(6):1172.
doi: 10.3390/antiox12061172.

From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs

Gina Cavaliere  1   2 , Fabiano Cimmino  2   3 , Giovanna Trinchese  3 , Angela Catapano  2   3 , Lidia Petrella  3 , Margherita D'Angelo  3 , Lucio Lucchin  4 , Maria Pina Mollica  2   3   5
Affiliations
Review

From Obesity-Induced Low-Grade Inflammation to Lipotoxicity and Mitochondrial Dysfunction: Altered Multi-Crosstalk between Adipose Tissue and Metabolically Active Organs

Gina Cavaliere et al. Antioxidants (Basel). .

Abstract

Obesity is a major risk factor for several metabolic diseases, including type 2 diabetes, hyperlipidemia, cardiovascular diseases, and brain disorders. Growing evidence suggests the importance of inter-organ metabolic communication for the progression of obesity and the subsequent onset of related disorders. This review provides a broad overview of the pathophysiological processes that from adipose tissue dysfunction leading to altered multi-tissue crosstalk relevant to regulating energy homeostasis and the etiology of obesity. First, a comprehensive description of the role of adipose tissue was reported. Then, attention was turned toward the unhealthy expansion of adipose tissue, low-grade inflammatory state, metabolic inflexibility, and mitochondrial dysfunction as root causes of systemic metabolic alterations. In addition, a short spot was devoted to iron deficiency in obese conditions and the role of the hepcidin-ferroportin relationship in the management of this issue. Finally, different classes of bioactive food components were described with a perspective to enhance their potential preventive and therapeutic use against obesity-related diseases.

Keywords: adipose tissue dysfunction; bioactive compounds; hypertrophy adipocytes; metabolic diseases; mitochondria; neurodegenerative disorders.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Unhealthy expansion of adipose tissue impacts mitochondrial function in metabolically active organs. ① In the obese condition, there is an unhealthy expansion of adipose tissue characterized by hypertrophic adipocytes that release numerous adipokines. Among these cytokines: MCP-1 (monocyte chemoattractant protein-1) attracts monocytes responsible for macrophage infiltration into adipose tissue and worsens chronic low-grade inflammation; TNF-α (tumor necrosis factor) with pleiotropic action increases inflammation and oxidative stress by modulating the Nf-KB pathway and mitochondrial capacity; LPS (lipopolysaccharide) derived from gut-dysbiosis contributes to systemic low-grade inflammation; IL-6 (interleukin-6) is responsible for hepcidin synthesis causing iron deficiency and ferroptosis; and finally, these adipokines impact mitochondrial function both in peripheral organs (liver, skeletal muscle, heart) and the brain. ② This context leads to increased neuroinflammation, insulin resistance, and lipotoxicity that worsen health conditions in obese subjects. ③ Some bioactive food components are able to counteract these pathological conditions through a reduction in fat depots and inflammation and an improvement in mitochondrial function with increased respiratory capacity, biogenesis, and dynamics and decreased ROS production.
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