Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study

Schnurr, Theresia M.; Jakupović, Hermina; Carrasquilla, Germán D.; Ängquist, Lars; Grarup, Niels; Sørensen, Thorkild I A; Tjønneland, Anne; Overvad, Kim; Pedersen, Oluf; Hansen, Torben; Kilpeläinen, Tuomas O.

doi:10.1007/s00125-020-05140-5

Cited by 147 publications

(99 citation statements)

References 27 publications

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“…Obesity has become an epidemic concern and brought on global public health consequences, Over one third of U.S. adults suffer from obesity ( 1 ), even 20–30% of entire populations have become obese in only 50 years ( 2 ), causing a series of severe comorbidities; for example, obesity was associated with a five-fold risk of type 2 diabetes regardless of genetic predisposition ( 3 ). Ranging from drugs to calorie restriction, the existing anti-obesity ways don’t yield the desired effect, among which white adipose tissue-browning intensified the interests in uncovering the underlying mechanisms due to its therapeutic potential for the remedy of metabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis

Tang

et al. 2021

Front. Endocrinol.

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BackgroundPrevious studies had suggested that electroacupuncture (EA) can promote white adipose tissue (WAT) browning to counter obesity. But the mechanism was still not very clear.AimIn this study, we aim to study the effect of EA on promoting inguinal WAT (iWAT) browning and its possible mechanism.MethodThree-week-old rats were randomly divided into a normal diet (ND) group and a high-fat diet (HFD) group. After 10 weeks, the HFD rats were grouped into HFD + EA group and HFD control group. Rats in the EA group were electro-acupunctured for 4 weeks on Tianshu (ST25) acupoint under gas anesthesia with isoflurane, while the rats in HFD group were under gas anesthesia only. Body weight and cumulative food intake were monitored, and H&E staining was performed to assess adipocyte area. The effect of EA on WAT was assessed by qPCR, immunoblotting, immunoprecipitation and Co-immunoprecipitation. Mitochondria were isolated from IWAT to observe the expression of mitochondrial transcription factor A (TFAM).ResultsThe body weight, WAT/body weight ratio and cumulative food consumption obviously decreased (P < 0.05) in the EA group. The expressions of brown adipose tissue (BAT) markers were increased in the iWAT of EA rats. Nevertheless, the mRNA expressions of WAT genes were suppressed by 4-week EA treatment. Moreover, EA increased the protein expressions of SIRT-1, PPARγ, PGC-1α, UCP1 and PRDM16 which trigger the molecular conversion of iWAT browning. The decrease of PPARγ acetylation was also found in EA group, indicating EA could advance WAT-browning through SIRT-1 dependent PPARγ deacetylation pathway. Besides, we found that EA could activate AMPK to further regulate PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis.ConclusionIn conclusion, EA can remodel WAT to BAT through inducing SIRT-1 dependent PPARγ deacetylation, and regulating PGC-1α-TFAM-UCP1 pathway to induce mitochondrial biogenesis. This may be one of the mechanisms by which EA affects weight loss.

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Section: Introductionmentioning

confidence: 99%

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis

Tang

et al. 2021

Front. Endocrinol.

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“…The number of obese and elderly people is constantly growing in industrialized countries. Obesity and aging are independent risk factors of Type 2 diabetes (T2D) [ 1 , 2 ]. Thus, the number of T2D people is increasing at an alarming rate and imposes a major health and economic burden on industrialized countries [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Insights and Mechanisms of Lipotoxicity-Driven Insulin Resistance

Lair

Laurens

Bosch

et al. 2020

IJMS

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A large number of studies reported an association between elevated circulating and tissue lipid content and metabolic disorders in obesity, type 2 diabetes (T2D) and aging. This state of uncontrolled tissue lipid accumulation has been called lipotoxicity. It was later shown that excess lipid flux is mainly neutralized within lipid droplets as triglycerides, while several bioactive lipid species such as diacylglycerols (DAGs), ceramides and their derivatives have been mechanistically linked to the pathogenesis of insulin resistance (IR) by antagonizing insulin signaling and action in metabolic organs such as the liver and skeletal muscle. Skeletal muscle and the liver are the main sites of glucose disposal in the body and IR in these tissues plays a pivotal role in the development of T2D. In this review, we critically examine recent literature supporting a causal role of DAGs and ceramides in the development of IR. A particular emphasis is placed on transgenic mouse models with modulation of total DAG and ceramide pools, as well as on modulation of specific subspecies, in relation to insulin sensitivity. Collectively, although a wide number of studies converge towards the conclusion that both DAGs and ceramides cause IR in metabolic organs, there are still some uncertainties on their mechanisms of action. Recent studies reveal that subcellular localization and acyl chain composition are determinants in the biological activity of these lipotoxic lipids and should be further examined.

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“…Indeed, secretion of adiponectin, leptin and other factors by adipose tissue can induce insulin resistance, thereby promoting diabetes [ 298 ]. Furthermore, a recent cohort study on a large Danish population concluded that the impact of obesity on diabetes risk is more important than genetics [ 299 ].…”

Section: Lifestyle Factorsmentioning

confidence: 99%

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

Jentzsch

Davis

Djamgoz

2020

Cancers

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The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.

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Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study

Cited by 147 publications

References 27 publications

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis

Electroacupuncture Regulates Inguinal White Adipose Tissue Browning by Promoting Sirtuin-1-Dependent PPARγ Deacetylation and Mitochondrial Biogenesis

Novel Insights and Mechanisms of Lipotoxicity-Driven Insulin Resistance

Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

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