Pathways from obesity to diabetes

Jp, Felber; Golay, Alain

doi:10.1038/sj.ijo.0802126

Cited by 183 publications

(153 citation statements)

References 33 publications

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“…5,6 Indeed, muscle impairments in insulin-mediated glucose transport, glycogen synthesis and glucose oxidative pathways are the central features of individuals at high risk for type 2 diabetes, notably in the lean normoglycemic offspring of diabetic patients and in obese patients. 7,8 As these population groups also present elevated plasma concentrations of fatty acids and amino acids, [9][10][11] these substrates or their metabolitesFby interfering with the uptake and metabolism of glucose in skeletal muscleFare thought to play a central role in the onset of insulin resistance. 12 Furthermore, there is also evidence that as chronic hyperglycemia develops, the oversupply of glucose could also, by inhibiting fatty acid oxidation, lead to the accumulation of intramyocellular lipid metabolites that further inhibit glucose uptake/metabolism and hence exacerbate the state of insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

et al. 2004

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Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely:(i) the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport), (ii) the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recently (iii) the stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes).This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity.

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Section: Introductionmentioning

confidence: 99%

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

et al. 2004

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“…30 kgam 2 ). 3 Increasing obesity trends pose a signi®cant concern as serious comorbities have been linked with obesity, 4 the most common being diabetes mellitus, 5,6 hypertension and cardiovascular disease. 7 Associations have also been reported with osteoarthritis, 8,9 gallbladder disease, 10 and certain types of cancer.…”

Section: Introductionmentioning

confidence: 99%

The health status of obese individuals in Canada

Trakas

Singh

et al. 2001

Int J Obes

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long-term residents of hospitals or residential care facilities. The sub-sample used in this analysis consisted of 38 151 respondents (52.4% male) between the ages of 20 and 64 y, excluding pregnant women. Health Utilities Index-Mark III (HUI3) scores were used to de®ne normal weight (body mass index (BMI) 19 ± 24.9 kgam 2 ), overweight (BMI 25 ± 29.9 kgam 2 ), obese (BMI 30 ± 34.9 kgam 2 ), and morbidly obese (BMI ! 35 kgam 2 ) individuals. HUI3 scores were age-and gender-standardized. RESULTS: The overall prevalence of obesity (BMI ! 30 kgam 2 ) in this Canadian population was 13.3%. The average difference in HUI3 scores between normal weight and morbidly obese respondents was 0.04 (P`0.001). Statistically signi®cant (P`0.05) differences across BMI categories were found in each of the eight component attributes of the HUI3. The attributes with the most substantial difference between normal and obese patients were cognition, mobility and pain. All demonstrated a ! 2-fold increase in the proportion of individuals in poorer classi®cations of health when normal weight respondents were compared with the morbidly obese. The magnitude of the decrement in utility ratings associated with obesity was comparable with other chronic non-cardiovascular conditions such as migraine or colitis. CONCLUSION:The results indicate that changes in self-rated health status appear to be due to signi®cant changes across several relevant domain attributes. Obesity has a signi®cant impact on both quality of life and health.

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“…O besity is a chronic pathological condition and a risk factor for type 2 diabetes and cardiovascular disease (1)(2)(3)(4). Several studies have shown that visceral obesity in particular is strongly associated with insulin resistance, hyperglycemia, dyslipidemia, and hypertension.…”

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confidence: 99%

Omentin Plasma Levels and Gene Expression Are Decreased in Obesity

et al. 2007

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Central obesity and the accumulation of visceral fat are risk factors for the development of type 2 diabetes and cardiovascular disease. Omentin is a protein expressed and secreted from visceral but not subcutaneous adipose tissue that increases insulin sensitivity in human adipocytes. To determine the impact of obesity-dependent insulin resistance on the regulation of two omentin isoforms, gene expression and plasma levels were measured in lean, overweight, and obese subjects. Omentin 1 was shown to be the major circulating isoform in human plasma. Lean subjects had significantly higher plasma omentin 1 levels than obese and overweight subjects. In addition, higher plasma omentin 1 levels were detected in women compared with men. Plasma omentin 1 levels were inversely correlated with BMI, waist circumference, leptin levels, and insulin resistance as measured by homeostasis model assessment and positively correlated with adiponectin and HDL levels. Both omentin 1 and omentin 2 gene expression were decreased with obesity and were highly correlated with each other in visceral adipose tissue. In summary, decreased omentin levels are associated with increasing obesity and insulin resistance. Therefore, omentin levels may be predictive of the metabolic consequences or co-morbidities associated with obesity.

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Pathways from obesity to diabetes

Cited by 183 publications

References 33 publications

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

The health status of obese individuals in Canada

Omentin Plasma Levels and Gene Expression Are Decreased in Obesity

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