Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

Armani, Andrea M.; Berry, Alessandra; Cirulli, Francesca; Caprio, Massimiliano

doi:10.1096/fj.201601125rrr

Cited by 56 publications

(42 citation statements)

References 195 publications

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“…Moreover, adipose tissue-specific dysfunctions with impact on the development of metabolic syndrome and deleterious effects on whole-body energy homeostasis are also related to aging [17]. Of importance, key processes of adipose tissue physiology affect molecular pathways that regulate lifespan [18].…”

Section: Adipose Metabolism and Lifespanmentioning

confidence: 99%

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Schosserer

Grillari²,

Wolfrum

et al. 2017

Gerontology

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Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time. Elevated oxidative stress is also found in metabolic diseases such as obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of the energy homeostasis is also associated with aging, and many age-related genes also control energy metabolism, with the adipose organ, comprising white, brite, and brown adipocytes, as an important metabolic player in the regulation of whole-body energy homeostasis. This review summarizes transformations in the adipose organ upon aging and cellular senescence and sheds light on the reallocation of fat mass between adipose depots, on the metabolism of white and brown adipose tissue, on the regenerative potential and adipogenic differentiation capacity of preadipocytes, and on alterations in mitochondria and bioenergetics. In conclusion, the aging process is a lifelong, creeping process with gradual decline in (pre-)adipocyte function over time. Thus, slowing down the accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent preadipocytes as well as blocking deleterious compounds of the senescent secretome are protective measures to maintain a lasting state of health at old age.

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Section: Adipose Metabolism and Lifespanmentioning

confidence: 99%

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Schosserer

Grillari²,

Wolfrum

et al. 2017

Gerontology

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“…In addition to genetic mechanisms, the continuous and excessive exposure to energy‐dense foods paired with a sedentary lifestyle has driven the obesity pandemic . White adipose tissue (WAT) is the primary site for energy storage and a dynamic endocrine organ secreting a range of bioactive molecules (adipokines, lipokines, and extracellular vesicles) to communicate with other cell types, thereby exerting diverse local and systemic effects with a major relevance on whole‐body homeostasis . Upon exceeding its expansion capacity by an enlargement in the size of adipocytes (hypertrophy), an increase in the number of adipocytes (hyperplasia) or both, WAT becomes dysfunctional and promotes the recruitment of immune cells, which ultimately leads to a low‐grade inflammatory state .…”

Section: Introductionmentioning

confidence: 99%

“…[4,5] White adipose tissue (WAT) is the primary site for energy storage and a dynamic endocrine organ secreting a range of bioactive molecules (adipokines, lipokines, and extracellular vesicles) to communicate with other cell types, thereby exerting diverse local and systemic effects with a major relevance on whole-body homeostasis. [6,7] Upon exceeding its expansion capacity by an enlargement in the size of adipocytes (hypertrophy), an increase in the number of adipocytes (hyperplasia) or both, WAT becomes dysfunctional and promotes the recruitment of immune cells, which ultimately leads to a low-grade inflammatory state. [8,9] Self-sustained lipolysis orchestrates the accumulation of monocytederived macrophages in the obese WAT, [10] where they polarize or switch from an M2 anti-inflammatory phenotype toward an M1 proinflammatory phenotype.…”

Section: Introductionmentioning

confidence: 99%

Monounsaturated Fatty Acids in a High‐Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome

Paz

Naranjo

López

et al. 2019

Molecular Nutrition Food Res

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Scope Obesity is a principal causative factor of metabolic syndrome. Niacin potently regulates lipid metabolism. Replacement of saturated fatty acids by MUFAs or inclusion of omega‐3 long‐chain PUFAs in the diet improves plasma lipid levels. However, the potential benefits of niacin in combination with MUFAs or omega‐3 long‐chain PUFAs against white adipose tissue (WAT) dysfunction in the high fat diet (HFD)‐induced metabolic syndrome are unknown. Methods and results Male Lepob/obLDLR−/− mice are fed a chow diet or HFDs based on milk cream (21% kcal), olive oil (21% kcal), or olive oil (20% kcal) plus 1% kcal from eicosapentaenoic and docosahexaenoic acids, including immediate‐release niacin (1% w/v) in drinking water, for 8 weeks. Mice are then phenotyped. Dietary MUFAs are identified as positive regulators of adipose NAD+ signaling pathways by triggering NAD+ biosynthesis via the salvage pathway. This coexists with overexpression of genes involved in recognition of NAD+ and fatty acids, a surrounding lipid environment dominated by exogenous oleic acid and an alternatively activated macrophage profile, which culminate in a healthy expansion of WAT and improvement of several hallmarks that typify the metabolic syndrome. Conclusion Niacin in combination with dietary MUFAs can favor WAT homeostasis in the development of HFD‐induced obesity and metabolic syndrome.

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“…Obesity is related to the development of metabolic dysfunctions (Armani et al. ), which has been described in liver (Ban et al. ), heart (Hamzeh et al.…”

Section: Introductionmentioning

confidence: 99%

“…Obesity is related to the development of metabolic dysfunctions (Armani et al 2017), which has been described in liver (Ban et al 2016), heart (Hamzeh et al 2017), and kidney (Whaley-Connell and Sowers 2017), collectively increasing the risk of cardiovascular disease and mortality. However, particularly in the recent decade, skeletal muscle dysfunction has been increasingly recognized as another detrimental effect of obesity and is characterized by a decrease in muscle strength and reduced ability to endure fatigue (Jurca et al 2004;Tomlinson et al 2014;Rastelli et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin

et al. 2018

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Exercise regimens may have differing effects in the presence of obesity. In addition to being fat derived, adiponectin has recently been described as a myokine that regulates insulin sensitivity, which may link to exercise‐related metabolic benefits in obesity. Whether skeletal muscle adiponectin varies in different exercise modalities is unclear. This study investigated the comparative effects of 10 weeks of endurance constant‐moderate intensity exercise (END) with high intensity interval training (HIIT), on metabolic outcomes, including muscle adiponectin in a mouse model of diet‐induced obesity. Ten‐week‐old male C57BL/6 mice were fed a high‐fat diet (HFD) (45% FAT) or standard CHOW diet ab libitum and underwent one of three training regimes: (1) no exercise, (2) END, or (3) HIIT (8 bouts of 2.5 min with eight periods of rest of 2.5 min) for 10 weeks (3 × 40 min sessions/week). Chow‐fed mice acted as controls. Compared with HFD alone, both training programs similarly protected against body weight gain (HFD = 45 ± 2; END = 37 ± 2; HIIT = 36 ± 2 g), preserved lean/fat tissue mass ratio (HFD = 0.64 ± 0.09; END = 0.34 ± 0.13; HIIT = 0.33 ± 0.13), and improved blood glucose excursion during an insulin tolerance test (HFD = 411 ± 54; END = 350 ± 57; HIIT = 320 ± 66 arbitrary units [AU]). Alterations in fasting glycemia, insulinemia, and AST/ALT ratios were prevented only by END. END, but not HIIT increased skeletal muscle adiponectin mRNA (14‐fold; P < 0.05) and increased protein content of high molecular weight (HMW) adiponectin (3.3‐fold), whereas HIIT induced a milder increase (2.4‐fold). Compared with HFD, neither END nor HIIT altered circulating low (LMW) or high (HMW) molecular weight adiponectin forms. Furthermore, only END prevented the HFD downregulation of PGC1α (P < 0.05) mRNA levels downstream of muscle adiponectin. These data show that different training programs affect muscle adiponectin to differing degrees. Together these results suggest that END is a more effective regimen to prevent HFD‐induced metabolic disturbances in mice.

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Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

Cited by 56 publications

References 195 publications

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Monounsaturated Fatty Acids in a High‐Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome

Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin

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