Role of Leptin in Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease (NAFLD), which affects about a quarter of the global population, poses a substantial health and economic burden in all countries, yet there is no approved pharmacotherapy to treat this entity, nor well-established strategies for its diagnosis. Its prevalence has been rapidly driven by increased physical inactivity, in addition to excessive calorie intake compared to energy expenditure, affecting both adults and children. The increase in the number of cases, together with the higher morbimortality that this disease entails with respect to the general population, makes NAFLD a serious public health problem. Closely related to the development of this disease, there is a hormone derived from adipocytes, leptin, which is involved in energy homeostasis and lipid metabolism. Numerous studies have verified the relationship between persistent hyperleptinemia and the development of steatosis, fibrinogenesis and liver carcinogenesis. Therefore, further studies of the role of leptin in the NAFLD spectrum could represent an advance in the management of this set of diseases.

Analysis of miRNAs Profiles in Serum of Patients With Steatosis and Steatohepatitis

“…Upregulated miR-200c-3p and miR-224-5p target the gene LEP and lead to its suppression ( Figure 7B and Supplementary Table 4 ). Hyperleptinemia has been shown to lead to the development of insulin resistance (the pathways of leptin and insulin cross), inhibition of lipid oxidation, and activation of lipogenesis by SREBP-1 in the liver ( Jiménez-Cortegana et al, 2021 ). Leptin can activate HSC, provoking the development of fibrosis ( Polyzos et al, 2011 ).…”

Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options

“…Adipose tissue caused by obesity can secrete diverse adipokines, such as leptin, adiponectin, and resistin, as well as proinflammatory cytokines, resulting in insulin resistance and chronic low-grade inflammation in different tissues, including liver tissue ( 29 ). For example, emerging evidence shows that leptin plays essential roles in cancer development by increasing tumor cell proliferation, metastasis, chemoresistance and promoting angiogenesis via binding its receptor to regulate many downstream signaling pathways ( 30 , 31 ), as well as promoting NASH and liver fibrosis ( 32 ). Obesity impacts adipocytes to secrete proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), and lipotoxicity induces hepatocyte death to activate Kupffer cells to produce those cytokines ( 33 ).…”

Possible Role of Leptin in Atopic Dermatitis: A Literature Review

“…plays a key role in the regulation of both energy metabolism and obesity, and also takes part in different diseases and processes, including (but not limited to) reproduction [36], autoimmunity [37], glucose metabolism [38], non-alcoholic fatty liver disease [39] or cancer [40,41].…”

“…Leptin is produced not only in WAT, a dynamic organ with multiple functions (e.g., the regulation of metabolism and energy balance, or its involvement in both inflammatory and immune responses), but also other tissues such as placenta [ 32 ], mammary gland [ 33 ], ovary [ 34 ] or pituitary gland [ 35 ]. Leptin plays a key role in the regulation of both energy metabolism and obesity, and also takes part in different diseases and processes, including (but not limited to) reproduction [ 36 ], autoimmunity [ 37 ], glucose metabolism [ 38 ], non-alcoholic fatty liver disease [ 39 ] or cancer [ 40 , 41 ].…”