Food Supply Trends

There have been changes in the national food supply that correspond to the increasing obesity prevalence in the United States. For example, data from the US Marketing System indicate that per capita calorie availability increased by 15 from 1970 to 1994, from 3300 kcal per capita in 1970 to 3800 kcal per capita in 1994 (10). This trend was coupled with a 22 increase in fats and oils added to the food supply, resulting in a doubling of added fat consumption, from 32 lb per capita in 1909 to 63...

Andrew J Teichtahl Anita E Wluka and Flavia M Cicuttini

Obesity is a risk factor for joint disease, in particular osteoarthritis, at both weight-bearing joints such as the knee, and non-weight bearing joints such as the carpometacarpal joint of the hand. Despite this, how obesity is mechanistically associated with joint disease is unclear. Both metabolic and biomechanical factors are likely to mediate the association between obesity and joint disease, although different joint tissues such as bone and cartilage are likely to differ in their response...

Leptin and the hygieneaffluence hypothesis in autoimmunity

Fewer infections and more autoimmunity, observed in affluent countries, lead us to postulate the so-called leptin hypothesis to explain this phenomenon (42). During the past century, in the industrialized world, the incidence of infections has diminished greatly because of improved hygienic conditions, better nutrition, vaccination, and the use of antibiotics (42). Interestingly, in affluent and more-developed societies, epidemio-logical studies have revealed a parallel increase in the...

Leptin modulation of adaptive immune response

Faggioni et al. (16) have reviewed the role of leptin in cell-mediated immunity, from data obtained working with ob ob mice. These mice have a decreased sensitivity of T-cells to activating stimuli. Furthermore, these animals show atrophy of lymphoid organs (4-6), with a decrease in the number of circulating T-cells and an increase in the number of monocytes. In addition, ob ob mice have a decrease in TNKCD4+ in the liver (39). The ability of leptin to prevent thymic atrophia is due to a direct...

Fetal Overnutrition Pathway

In addition to these effects of prenatal undernutrition, it is well recognized that the fetuses of diabetic mothers are born with relative obesity, suggesting a separate pathway linking prenatal nutrition with later risk of metabolic disease. Maternal hyperglycemia leads to fetal hyperglycemia and fetal hyperinsulinemia, which promotes excessive fat deposition during the third trimester. The degree of subcutaneous adiposity is increased even under conditions of subclinical maternal...

Acquired generalized lipodystrophy

Acquired generalized lipodystrophy (AGL) is another rare disorder and has been reported in approx 80 patients (47). It is characterized by selective loss of AT from large regions of the body occurring after birth. AT loss usually involves face, trunk, and extremities, and sometimes also spreads to the palms and soles. Intra-abdominal fat may also be lost, although retro-orbital and bone marrow fat are generally well preserved. The loss of AT may occur precipitously, within a few weeks, or may...

Adiponectin as Insulin Sensitizing Hormone

The role of adiponectin as an important regulator of insulin sensitivity was first reported by Fruebis and colleagues in 2001 (16). The authors found that injection of a COOH-terminal globular adiponectin into mice acutely decreased postprandial blood glucose levels and enhance lipid clearance via increasing fatty acid -oxidation in skeletal muscles. This observation was subsequently confirmed and extended by several pharmacological studies using different forms of recombinant adiponectin....

Arvind Batra and Britta Siegmund

Leptin is a 16-kDa protein, predominantly produced by adipose tissue with serum leptin concentrations correlating to body fat mass. Initially described as a regulator of appetite, it is now well established that this mediator exerts pro-inflammatory effects on various immune as well as nonimmune cells. In vitro as well as in vivo studies suggest an involvement of leptin in the regulation of intestinal inflammation. The data leading to this finding are the subject of discussion in this chapter....

Congenital generalized lipodystrophy from mutations in BSCL2 and AGPAT2

Since the first case description of CGL, an autosomal recessive disorder, by Berardinelli and Seip (10,11), some 300 cases have been reported so far. Although described in patients of various ethnic origins, significant clusters of patients seem to be localized to some regions in Brazil and Lebanon. Affected patients have near-complete absence of subcutaneous AT from birth, leading to marked prominence of muscles and veins. During childhood, they are noted to have a voracious appetite,...

Mammary Adipose Tissue and Breast Cancer

It is known that inflammation can promote tumorigenesis. There is compelling evidence indicating that both normal mammary gland development and breast cancer growth depend, in part, on microenvironment, of which adipose tissue is a key component (ref. 28 and references therein). Interestingly, the mammary gland microenvironment during postlactational involution shares similarities with inflammation, which may be promotional for breast cancer development associated with pregnancy (54). Recently,...

Female Breast Cancer

Many epidemiological studies since the 1970s have assessed the association between anthropometric measures and female breast cancer occurrence and or prognosis (18,47). Early studies established that the association between body size and risk of breast cancer varied based on menopausal status that heavier women were at increased risk of postmenopausal, but not premenopausal, breast cancer (18). In fact, among pre-menopausal women, there is consistent evidence of a modest reduction in risk among...

Adiponectin as a potent antiinflammation adipocytokine

As already mentioned, adiponectin has multiple functions for prevention of metabolic diseases and cardiovascular diseases. More recently, adiponectin was shown to prevent liver fibrosis and some kinds of cancer such as endometrial cancer, breast cancer, and colon cancer, in animal models (29-32). Besides these well-characterized biological functions, recent evidence supports a strong anti-inflammatory function. We first reported that adiponectin strongly suppresses production of the potent...

George N Chaldakov Anton B Tonchev Nese Tuncel Pepa Atanassova and Luigi Aloe

Recently, the endocrine activity of adipose tissue cells has been intensively studied. In effect, a wide range of exported secretory proteins, dubbed adipokines, have been identified as constituents of the adipose proteome (adipokinome). Besides their effects on glucose and energy metabolism, adipokines are potent modulators of inflammation. This chapter provides a state-of-the-science review of adipokine-mediated paracrine signaling that may be implicated in the pathogenesis of...

Adipokines Inhibitory Yin and Stimulatory Yang Signals in Inflammation

Celsus's description (first century AD) of inflammation signs includes rubor et tumor cum calor et dolor. Inflammation is an essential biological response aiming at recovering from injury, wound healing being a paradigm of such a homeostatic phenomenon. However, what begins as a protective response becomes a damaging process in excess hence, inflammation is increasingly recognized as the underlying basis of a significant number of diseases. Recent studies based on a pangenomic approach in human...

Hypoadiponectinemia and Cancers

Low levels of plasma adiponectin are closely correlated with several obesity- and insulin resistance-related cancers. A strong inverse association between plasma adiponectin levels and the risk of both breast cancer and endometrial cancer has recently been reported in two case-control studies (99,100). Importantly, these associations are independent of adiposity, insulin resistance, and other classical risk factors. Another study by Miyoshi et al. has shown that breast cancers arising in women...

Leptin in endometriosis

Pelvic endometriosis (PE) is one of the most common benign gynecological diseases, characterized by implantation and growth of endometrial tissue in the pelvic peritoneum and associated with infertility and pain (34,35). The most accredited pathogenetic theory of endometriosis considers the transport of endometrial tissue to the peritoneal cavity throughout the tubes (retrograde menstruation), adherence to the peritoneal wall, followed by proliferation and formation of endometriotic lesions...

Recruitment of monocytes to adipose tissue in obesity

Although recent studies have established that obesity is associated with the accumulation of macrophages in adipose tissue of rodents and humans, the mechanisms that regulate this process are just being studied. The first step in the recruitment of mono-cytes to a tissue is the adhesion to endothelial cells. In human studies, obesity and impaired insulin sensitivity are associated with elevated circulating concentrations of cellular adhesion molecules, including ICAM-1, VCAM-1, and E-selectin...

Asthma and Obstructive Sleep Apnea

In a study of 33 patients with asthma who were followed for 1 yr after weight-loss surgery, all patients showed improvement in symptoms (severity and frequency) and a third of them had no episodes of asthma and were off all therapy during follow-up (44). Weigh loss also improves symptoms associated with obstructive sleep apnea (OSA). The seriousness of this problem is emphasized by the fact that the cost of medical care of obese patients with OSA has been estimated to be twice the cost of...

Leptin in multiple sclerosis

Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory disorder of the central nervous system (CNS) myelin. The most studied model of multiple sclerosis in animals is the EAE that can be induced in susceptible strains of mice by immunization with self-antigens derived from myelin. The disease is characterized by autoreactive T-cells that traffic to the brain and the spinal cord and injury myelin, with the result of chronic or relapsing-remitting paralysis, depending on the antigen...

Implications for change changing environments vs individuals

In response to growing concern over the obesity problem in the United States, in 2001 the US Surgeon General issued a report, A Call to Action to Prevent and Decrease Overweight and Obesity, advocating healthier school and workplace environments. Other position statements and guidelines issued by the Centers for Disease Control and Prevention, the Institute of Medicine (see Table 2), and the American Academy of Pediatrics have provided an initial framework for formulating and implementing...

Leptin in type 1 autoimmune diabetes

Leptin is involved in other autoimmune conditions (17). Leptin accelerates autoimmune diabetes in female NOD LtJ mice (18). Fluctuations in serum leptin levels have also been observed in a study performed by our group in an animal model of CD4+ T-cell-mediated autoimmune disease, such as T1D. Nonobese diabetic (NOD LtJ) female mice, spontaneously prone to the development of -cell autoimmunity, have higher serum leptin levels, as compared with NOD LtJ males and nonsusceptible strains of mice,...

Adipokines and Oxidative Stress

Changes in serum adipokine concentrations augment oxidative stress in patients with NASH. Most studies converge on CYP2E1, peroxisomal release of ROS, and mitochon-drial dysfunction. ROS and reactive nitrogen species (RNS) are generated by the parenchymal cells of the liver, Kupffer cells, and inflammatory cells, which further mobilize cellular defense mechanisms and contribute to liver injury and necrosis. The potential role of adiponectin as an antioxidant is mostly indirect. One study...

Visfatin

Visfatin is a recently discovered adipokine, which is apparently produced and secreted mainly by visceral WAT, with putative antidiabetogenic properties by binding to the insulin receptor and exerting an insulinomimetic effect both in vitro and in vivo (52,53). Visfatin was originally identified as pre-B-cell colony-enhancing factor (PBEF), a cytokine with increased presence in the bronchoalveolar lavage fluid of animal models of acute lung injury as well as in the neutrophils of septic...

Mechanisms of Kidney Damage in Adiposity

There are several biological mechanisms through which adiposity could lead to kidney damage (Table 1). Pathophysiology of increased microalbuminuria and proteinuria may include glomerular hyperfiltration, increased renal venous pressure, glomerular hypertrophy (due to mesangial cell hypertrophy and matrix production), and increased synthesis of vasoactive and fibrogenic substances (including angiotensin II, insulin, Altered vascular structure and function Enhanced renin-angiotensin-aldosterone...

Adipose tissue distribution in humans and adipocyte differentiation

Adipocytes Differentiation

In humans, unlike other organs such as the liver, heart, or lung, the AT does not have a well-defined tissue demarcation. Fat under the skin or dermis is referred to as subcutaneous AT, whether it lies under the skin of the abdomen, extremities, or other parts of the body. Fat found in the visceral cavity of the body is largely referred to as intraabdominal or omental AT. In humans, the subcutaneous (sc) and the omental forms are the two large AT depots that have been studied in detail, whereas...

Aimin Xu Yu Wang and Karen S L

Adiponectin is a glycosylated adipokine selectively secreted from adipocytes. The native adiponectin forms several oligomeric complexes, including trimer, hexamer, and high-molecular-weight (HMW) 12-18 multimers. In the past 5 yr, numerous clinical studies have demonstrated a close association between low plasma levels of adiponectin (hypoadiponectinemia) with obesity-related diseases, including dyslipidemia, atherosclerotic cardiovascular diseases, type II diabetes, hypertension, fatty liver,...

Leptin in rheumatoid arthritis

AIA is a model of immune-mediated joint inflammation induced by administration of methylated bovine serum albumin (mBSA) into the knees of immunized mice (21). The severity of arthritis in leptin- and leptin receptor-deficient mice was reduced in this model (22). The milder form of AIA seen in ob ob and db db mice, as compared with their controls, was accompanied by decreased synovial levels of interleukin (IL)-1P and TNF-a, decreased proliferative response to antigen of lymph node cells in...

Eugenia E Calle

The International Agency for Research on Cancer has classified the evidence of a causal link between adiposity and human cancer as sufficient for cancers of the colon, female breast (postmenopausal), endometrium, kidney (renal cell), and esophagus (adenocarcinoma). In addition to these cancers, more recent epidemiological evidence suggests that cancers of the liver and pancreas are obesity related, and that adiposity may also increase the risk for hematopoietic cancers and aggressive prostate...

Robert H Mak and Wai W Cheung

Cachexia is brought about by a synergistic combination of a dramatic decrease in appetite and an increase in metabolism of fat and lean body mass. This combination is found in a number of disorders including cancer, chronic kidney disease (CKD), AIDS, cystic fibrosis, chronic heart failure, rheumatoid arthritis, and Alzheimer's disease. Cachexia has a stronger correlation with survival than any other current measure of diseases such as AIDS, cancer, and CKD. The underlying mechanism of...

Adipose Tissue Hypertrophy and Inflammation

One of the most radical developments in obesity research in the past few years is recognition that low-level chronic inflammation and other forms of immune dysfunction are associated with excess adipose tissue, at least in humans and laboratory rodents (84,85). Chronic inflammation is believed to be one of several mechanisms linking obesity to increased risk of adult-onset cancer (86), type 2 diabetes (85), and atherosclerosis (87,88), although the causal relationships are far from clear (89)....

Adiposity vs Bone Formation

Aging of the human skeleton is characterized by decreased bone formation and bone mass. The decrease in bone volume associated with age-related osteopenia is accompanied by an increase in marrow adipose tissue as determined by histomorphometry (38,39). Adipogenesis is also observed in almost all conditions that lead to osteoporosis (40,41), such as ovariectomy (42), limb immobilization (43), alcoholism (44), and excessive treatment with glucocorticoids (45). Conversely, adipogenesis is...

Energy expenditure in cachexia

Energy expenditure is increased in cachexic patients with cancer and CKD. In patients with advanced pancreatic cancer, resting energy expenditure is increased, whereas total energy expenditure and physical activity levels are reduced (14). In patients with CKD, energy expenditure is related to inflammation. Resting energy expenditure correlated with surrogate markers of inflammation, such as C-reactive protein, and treatment of infection and subsequent resolution of elevated C-reactive protein...