The Impact of Adipose Tissue on Insulin Resistance in Acromegaly

Olarescu, Nicoleta Cristina; Bollerslev, Jens

doi:10.1016/j.tem.2016.02.005

Cited by 61 publications

(49 citation statements)

References 81 publications

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“…For example, as TBS is computed from DXA images, any image "noise" can influence the TBS evaluation and excessive soft tissue in the abdomen, overlying the region of interest, may reduce the TBS estimate. It is known that with treatment of acromegaly, although BMI remains unchanged, the patients do accumulate fat, predominantly in the central depots (20,41), and this can interfere with TBS estimates and lead to a measurement of a false decrease in TBS.…”

Section: Discussionmentioning

confidence: 99%

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

European Journal of Endocrinology

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Context: Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. Objective: The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. Results: Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both P < 0.01). The changes in BMD LS and TBS were not correlated (P = 0.87). The TBS change was found to be −4.5 % (±6.7; P = 0.003) in men and −0.3 % (±6.8; P = 0.85) in women (P = 0.063 for interaction men vs women). The mean BMD LS increased in men +4.2 g/cm 2 (±4.3; P < 0.001), but not in women +1.5 g/ cm 2 (±5.6; P = 0.36); (P = 0.073 for interaction). BMD increased in the ultradistal radius and total body (both P < 0.01).The increase in BMD LS was associated with a decrease in P1NP and CTX-1 (P < 0.001) and with lower P1NP and CTX-1 at the follow-up (P < 0.02). Conclusion: Treatment of acromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control.

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Section: Discussionmentioning

confidence: 99%

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Godang

Olarescu

Bollerslev

et al. 2016

European Journal of Endocrinology

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“…Congenital loss of global GH signaling increases insulin sensitivity and adiposity and may decrease the incidence of diabetes and cancer (21,22). Conversely, exposure to GH acutely (19) or chronically, in the setting of acromegaly, induces insulin resistance (23). Somewhat paradoxically, adult-onset of GH deficiency also predisposes to fatty liver and NASH (24), possibly by a different mechanism via direct effects on hepatic DNL (25).…”

Section: Introductionmentioning

confidence: 99%

Adipocyte JAK2 mediates aging-associated metabolic liver disease and progression to hepatocellular carcinoma

Corbit

Wilson

Lowe

et al. 2019

Preprint

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Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are liver manifestations of the metabolic syndrome and can progress to hepatocellular carcinoma (HCC). Loss of Growth Hormone (GH) signaling is reported to predispose to NAFLD and NASH through direct actions on the liver. Here, we report that aged mice lacking hepatocyte Jak2 (JAK2L), an obligate transducer of Growth Hormone (GH) signaling, spontaneously develop the full spectrum of phenotypes found in patients with metabolic liver disease, beginning with insulin resistance and lipodystrophy and manifesting as NAFLD, NASH and even HCC, independent of dietary intervention. Remarkably, insulin resistance, metabolic liver disease, and carcinogenesis are prevented in JAK2L mice via concomitant deletion of adipocyte Jak2 (JAK2LA). Further, we demonstrate that GH increases hepatic lipid burden but does so indirectly via signaling through adipocyte JAK2. Collectively, these data establish adipocytes as the mediator of GH-induced metabolic liver disease and carcinogenesis. In addition, we report a new spontaneous model of NAFLD, NASH, and HCC that recapitulates the natural sequelae of human insulin resistance-associated disease progression. The work presented here suggests a attention be paid towards inhibition of adipocyte GH signaling as a therapeutic target of metabolic liver disease.

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“…Insulin resistance is characterized by the accumulation of intrahepatic lipids due to an imbalance in lipid metabolism and free‐fatty acid oxidation . Meanwhile, adipose tissue is recognized as a key contributor to systemic insulin resistance . Thus, understanding the mechanism by which MR improves lipid metabolism might uncover novel potential therapeutic strategies for patients with diabetes and metabolic diseases.…”

Section: Mr and Diabetesmentioning

confidence: 99%

“…[70][71][72] Meanwhile, adipose tissue is recognized as a key contributor to systemic insulin resistance. [73] Thus, understanding the mechanism by which MR improves lipid metabolism might uncover novel potential therapeutic strategies for patients with diabetes and metabolic diseases.…”

Section: Lipid Metabolism and Pentose Phosphate Pathwaymentioning

confidence: 99%

Metabolic Regulation of Methionine Restriction in Diabetes

Yin

Ren

Chen

et al. 2018

Molecular Nutrition Food Res

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Although the effects of dietary methionine restriction have been investigated in the physiology of aging and diseases related to oxidative stress, the relationship between methionine restriction (MR) and the development of metabolic disorders has not been explored extensively. This review summarizes studies of the possible involvement of dietary methionine restriction in improving insulin resistance, glucose homeostasis, oxidative stress, lipid metabolism, the pentose phosphate pathway (PPP), and inflammation, with an emphasis on the fibroblast growth factor 21 and protein phosphatase 2A signals and autophagy in diabetes. Diets deficient in methionine may be a useful nutritional strategy in patients with diabetes.

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The Impact of Adipose Tissue on Insulin Resistance in Acromegaly

Cited by 61 publications

References 81 publications

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

Adipocyte JAK2 mediates aging-associated metabolic liver disease and progression to hepatocellular carcinoma

Metabolic Regulation of Methionine Restriction in Diabetes

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